US20120244133A1 - Methods of growing tumor infiltrating lymphocytes in gas-permeable containers - Google Patents

Methods of growing tumor infiltrating lymphocytes in gas-permeable containers Download PDF

Info

Publication number
US20120244133A1
US20120244133A1 US13/424,646 US201213424646A US2012244133A1 US 20120244133 A1 US20120244133 A1 US 20120244133A1 US 201213424646 A US201213424646 A US 201213424646A US 2012244133 A1 US2012244133 A1 US 2012244133A1
Authority
US
United States
Prior art keywords
til
cells
gas permeable
tumor tissue
tissue sample
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US13/424,646
Other languages
English (en)
Inventor
Steven A. Rosenberg
Mark E. Dudley
David Stroncek
Marianna Sabatino
Jianjian Jin
Robert Somerville
John R. Wilson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
US Department of Health and Human Services
Wilson Wolf Manufacturing Corp
Original Assignee
US Department of Health and Human Services
Wilson Wolf Manufacturing Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by US Department of Health and Human Services, Wilson Wolf Manufacturing Corp filed Critical US Department of Health and Human Services
Priority to US13/424,646 priority Critical patent/US20120244133A1/en
Assigned to THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES, WILSON WOLF MANUFACTURING CORPORATION reassignment THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SABATINO, Marianna, JIN, JIANJIAN, STRONCEK, David, DUDLEY, MARK E., SOMERVILLE, ROBERT, WILSON, JOHN R., ROSENBERG, STEVEN A.
Publication of US20120244133A1 publication Critical patent/US20120244133A1/en
Priority to US15/375,289 priority patent/US20170152478A1/en
Priority to US16/211,859 priority patent/US11401503B2/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/0005—Vertebrate antigens
    • A61K39/0011—Cancer antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C12N5/0638—Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515—Animal cells
    • A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
    • A61K2239/57—Skin; melanoma
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2302—Interleukin-2 (IL-2)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2315—Interleukin-15 (IL-15)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/50—Cell markers; Cell surface determinants
    • C12N2501/515—CD3, T-cell receptor complex
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system cells

Definitions

  • TIL tumor infiltrating lymphocytes
  • An embodiment of the invention provides a method of promoting regression of cancer in a mammal comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining tumor infiltrating lymphocytes (TIL) from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and administering the expanded number of TIL to the mammal.
  • TIL tumor infiltrating lymphocytes
  • Another embodiment of the invention provides a method of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining TIL from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells.
  • Still another embodiment of the invention provides a method of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy comprising obtaining a tumor tissue sample from the mammal; obtaining TIL from the tumor tissue sample; expanding the number of TIL in a gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells.
  • Another embodiment of the invention provides a method of promoting regression of cancer in a mammal comprising obtaining a tumor tissue sample from the mammal; obtaining TIL from the tumor tissue sample; expanding the number of TIL in a gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and administering the expanded number of TIL to the mammal.
  • FIG. 1A is a graph showing the numbers of TIL produced by 10 tumor fragments from eight tumor samples in 24-well plates (diamonds) and G-Rex10 flasks (squares). For each individual tumor sample, 10 fragments were seeded into a 24-well plate at 1 piece per well and 10 fragments were seeded into a single G-Rex 10 flask. Cells were harvested by 7 to 23 days of culture, pooled if collected from 24-well plate, and counted. A total of 8 samples were tested.
  • FIG. 1C is a graph showing the total number of TIL produced by 7 to 23 days of culture of 5, 10, 20 and 30 tumor fragments in G-Rex10 flasks.
  • the data were normalized using the number of cells produced in G-Rex10 flasks with 10 fragments.
  • the total number TIL produced in each G-Rex10 flask was divided by the number of TIL produced by each G-Rex10 flask seeded with 10 tumor fragments from the same patient.
  • An embodiment of the invention provides a method of promoting regression of cancer in a mammal comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining tumor infiltrating lymphocytes (TIL) from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and administering the expanded number of TIL to the mammal.
  • TIL tumor infiltrating lymphocytes
  • inventive methods provide numerous advantages. For example, methods of promoting regression of cancer and obtaining an expanded number of TIL using gas permeable containers are simpler, less labor-intensive, use less reagents, and can be performed using simpler equipment than procedures using non-gas permeable containers (e.g., T-flasks (e.g., T-175 flasks), bags, and multi-well plates).
  • non-gas permeable containers e.g., T-flasks (e.g., T-175 flasks), bags, and multi-well plates.
  • gas permeable containers may advantageously protect the cells from microbial contamination more effectively than non-gas permeable containers which may be “open” systems.
  • methods using gas permeable containers may advantageously reduce the number of containers that are used compared to methods using non-gas permeable containers, thereby reducing the amount of labor necessary to carry out the methods and also reducing the risk of microbial contamination.
  • producing cells in gas permeable containers may be more suitable for compliance with the current manufacturing practice (cGMP) conditions that are required for, e.g., Phase III clinical trials.
  • cGMP current manufacturing practice
  • methods using gas-permeable containers advantageously reduce the final culture volume to lower than that obtained with non-gas permeable containers, which advantageously lowers the incubator capacity required to grow the cells, reduces the amount of reagents (e.g., cell culture medium and additives) necessary to grow the cells, and simplifies the equipment and/or procedures for concentrating and washing the cells.
  • the inventive methods is that the cells may be fed less frequently in gas-permeable containers (e.g., about every three to four days) than in non-gas permeable containers (e.g., every other day), particularly when the cells and/or tumor tissue sample are cultured submerged under at least about 1.3 cm of cell culture medium in a gas permeable container.
  • cells in gas permeable containers may be handled less frequently than cells in non-gas permeable containers (e.g., bags), which may minimize disturbance of the tumor fragment and provide more reproducible TIL growth.
  • one or more aspects (e.g., but not limited to, culturing and/or expanding) of the inventive methods may be automatable.
  • the development of a simpler, less expensive, and less labor-intensive method to generate clinically effective TIL is believed to advantageously aid in the more widespread use of adoptive cell therapy and permit the delivery of therapeutically effective TIL to more patients in a shorter time period.
  • Faster and more efficient adoptive cell therapy may allow patients to be treated more quickly when the disease is at an earlier, less progressive stage, which increases the likelihood that more patients will respond positively to treatment.
  • inventive methods may also make it possible to treat certain patients who previously may not have been successfully treated because sufficient numbers of TIL were not generated due to the technical and logistical complexities of methods that do not use gas permeable flasks. Accordingly, the inventive methods advantageously may make it possible to treat or prevent a wider variety of cancers and, therefore, treat a larger number of patients.
  • the method comprises obtaining a tumor tissue sample from the mammal.
  • the tumor tissue sample can be obtained from numerous sources, including but not limited to tumor biopsy or necropsy.
  • the tumor tissue sample may be obtained from any cancer, including but not limited to any of the cancers described herein.
  • the cancer is melanoma.
  • the tumor tissue sample may be obtained from any mammal.
  • the tumor tissue sample is obtained from a human.
  • the tumor tissue sample may be a tumor tissue fragment.
  • the tumor tissue sample may be fragmented, e.g., by dissection, to provide a tumor tissue fragment.
  • the tumor tissue sample may, optionally, be enzymatically or mechanically digested.
  • Suitable enzymes for fragmenting the tumor tissue sample include, but are not limited to, collagenase.
  • the tumor tissue sample is fragmented without digestion.
  • the tumor tissue fragment may be any suitable size.
  • the tumor tissue fragment has a size of about 1 mm 3 or less to about 8 mm 3 or larger, about 1 mm 3 to about 4 mm 3 , about 1 mm 3 to about 2 mm 3 , or about 1 mm 3 .
  • the method further comprises culturing the tumor tissue sample in a first gas permeable container containing cell medium therein.
  • the tumor tissue sample is cultured directly on the gas permeable material in the gas permeable container without digestion.
  • an enzymatically or mechanically digested tumor tissue sample may be cultured directly on the gas permeable material.
  • Any suitable cell medium may be used.
  • the cell culture medium may further comprise any suitable T-cell growth factor such as, e.g., interleukin (IL)-2.
  • the cell culture medium may optionally further comprise human AB serum.
  • the tumor tissue sample may contain TIL that are autologous to the patient. Culturing the tumor tissue sample may include culturing the TIL present in the tumor sample.
  • the method also comprises obtaining TIL from the tumor tissue sample.
  • the tumor tissue sample comprises TIL.
  • TIL present in the tumor tissue sample also begin to grow in the gas permeable container, e.g., on the gas permeable material.
  • TIL may be obtained from the tumor tissue sample in any suitable manner.
  • the first gas permeable container may be any suitable gas permeable container.
  • the first gas permeable container comprises a base, sides, and a cap.
  • the container preferably the base, may comprise a gas permeable support and a gas permeable material, e.g., a gas permeable membrane.
  • the gas permeable material may be positioned inside the container directly on the gas permeable support which comprises openings (e.g., channels) in fluid communication with ambient gas in order to facilitate gas exchange between the interior of the container and the ambient gas.
  • the cap may comprise a vent and/or a port (e.g., an access port).
  • the access port may have an opening greater than about 1 mm to about 1 cm (e.g., greater than about 1 mm or greater than about 1 cm).
  • An access port with an opening greater than about 1 mm to about 1 cm may advantageously eliminate or reduce disturbance of the TIL.
  • the gas permeable container may comprise a vent or a vented port, which may be advantageous in the event that the temperature in the container drops during handling.
  • the first gas permeable container is a gas permeable container as described in U.S. Patent Application Publication No. 2005/0106717, which is incorporated herein by reference, and commercially available from Wilson Wolf Manufacturing Corporation (e.g., G-Rex10, GP200, G-Rex100, GP2000 containers) (New Brighton, Minn.).
  • the first gas permeable container may have any suitable cell medium volume capacity.
  • the first gas permeable container may have a medium volume capacity of about 40 mL or more; about 200 mL or more; about 500 mL or more; about 2,000 mL or more; or about 5,000 mL or more.
  • the tumor tissue sample and/or TIL may be cultured in any suitable volume of medium.
  • the tumor tissue sample and/or TIL are cultured submerged under a height of at least about 1.3 cm of cell culture medium. More preferably, the tumor tissue sample and/or TIL are cultured submerged under a height of at least about 2.0 cm of cell culture medium. Tumor tissue samples and/or TIL cultured on a gas permeable material submerged under a height of at least about 1.3 cm or a height of at least about 2.0 cm of medium may, advantageously, be handled and fed less frequently.
  • the first gas permeable container may provide any suitable surface area for the growth of the TIL.
  • the gas permeable container may have a surface area for growth of the TIL of about 10 cm 2 or more; about 100 cm 2 or more; or about 650 cm 2 or more.
  • the tumor tissue sample and/or TIL are cultured inside the first gas permeable container in contact with the gas permeable material and submerged under a suitable volume of culture medium. Culturing the tumor tissue sample and/or TIL in contact with the gas permeable material facilitates gas exchange between the cells and the ambient air. Facilitating gas exchange between the cells and the ambient air facilitates the respiration, growth, and viability of the cells. Moreover, the gas exchange across the gas permeable material can facilitate circulation of the medium (e.g., by convection and diffusion) within the container, which facilitates feeding of the TIL.
  • the medium e.g., by convection and diffusion
  • the method further comprises expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells.
  • the number of TIL is expanded using a ratio of about 1 TIL to at least about 20 feeder cells, about 1 TIL to at least about 25 feeder cells, about 1 TIL to at least about 50 feeder cells, about 1 TIL to at least about 100 feeder cells, about 1 TIL to at least about 200 feeder cells, e.g., a TIL-to-feeder cell ratio of about 1 to about 20, about 1 to about 25, about 1 to about 50, about 1 to about 100, or about 1 to about 200.
  • the second gas permeable container may be as described for the first container.
  • the cultured TIL are expanded, preferably, rapidly expanded.
  • Rapid expansion provides an increase in the number of TIL of at least about 50-fold (or 60-, 70-, 80-, 90-, or 100-fold, or greater) over a period of about 10 to about 14 days, preferably about 14 days. More preferably, rapid expansion provides an increase of at least about 200-fold (or 300-, 400-, 500-, 600-, 700-, 800-, 900-, or greater) over a period of about 10 to about 14 days, preferably about 14 days. Most preferably, rapid expansion provides an increase of at least about 1000-fold over a period of about 10 to about 14 days, preferably about 14 days. Preferably, rapid expansion provides an increase of about 1000-fold to about 2000-fold, e.g., about 1000-fold, about 1500-fold, or about 2.000-fold over a period of about 14 days.
  • TIL can be rapidly expanded using non-specific T-cell receptor stimulation in the presence of feeder cells (e.g., irradiated allogeneic feeder cells, irradiated autologous feeder cells, and/or artificial antigen presenting cells (e.g., K562 leukemia cells transduced with nucleic acids encoding CD3 and/or CD8)) and either interleukin-2 (IL-2) or interleukin-15 (IL-15), with IL-2 being preferred.
  • feeder cells e.g., irradiated allogeneic feeder cells, irradiated autologous feeder cells, and/or artificial antigen presenting cells (e.g., K562 leukemia cells transduced with nucleic acids encoding CD3 and/or CD8)
  • IL-2 interleukin-2
  • IL-15 interleukin-15
  • expanding the number of TIL uses about 1 ⁇ 10 9 to about 4 ⁇ 10 9 allogeneic feeder cells and/or autologous feeder cells, preferably about 2 ⁇ 10 9 to about 3 ⁇ 10 9 allogeneic feeder cells and/or autologous feeder cells.
  • the non-specific T-cell receptor stimulus can include, for example, about 30 ng/ml of OKT3, a mouse monoclonal anti-CD3 antibody (available from ORTHO-MCNEIL, Raritan, N.J. or MILTENYI BIOTECH, Auburn, Calif.).
  • TIL can be rapidly expanded by, for example, stimulation of the TIL in vitro with an antigen (one or more, including antigenic portions thereof, such as epitope(s), or a cell) of the cancer, which can be optionally expressed from a vector, such as an human leukocyte antigen A2 (HLA-A2) binding peptide, e.g., 0.3 ⁇ M MART-1:26-35 (27L) or gp100:209-217 (210M), in the presence of a T-cell growth factor, such as 300 IU/ml IL-2 or IL-15, with IL-2 being preferred.
  • HLA-A2 human leukocyte antigen A2
  • TIL tyrosinase cancer antigen
  • MAGE-A3, SSX-2 tyrosinase cancer antigen
  • VEGFR2 tyrosinase cancer antigen
  • the in vitro-induced TIL are rapidly expanded by re-stimulation with the same antigen(s) of the cancer pulsed onto HLA-A2-expressing antigen-presenting cells.
  • the TIL can be re-stimulated with, for example, irradiated, autologous lymphocytes or with irradiated HLA-A2+ allogeneic lymphocytes and IL-2, for example.
  • expanding the number of TIL may comprise using about 5,000 mL to about 10,000 mL of cell medium, preferably about 5,800 mL to about 8,700 mL of cell medium.
  • expanding the number of TIL uses no more than one type of cell culture medium.
  • Any suitable cell culture medium may be used, e.g., AIM-V cell medium (L-glutamine, 50 ⁇ g/ml streptomycin sulfate, and 10 ⁇ g/ml gentamicin sulfate) cell culture medium (Invitrogen, Carlsbad Calif.).
  • AIM-V cell medium L-glutamine, 50 ⁇ g/ml streptomycin sulfate, and 10 ⁇ g/ml gentamicin sulfate
  • the inventive methods advantageously reduce the amount of medium and the number of types of medium required to expand the number of TIL.
  • expanding the number of TIL may comprise feeding the cells no more frequently than every third or fourth day. Expanding the number of cells in a gas permeable container advantageously simplifies the procedures necessary to expand the number of cells by reducing the feeding frequency necessary to expand the cells.
  • the cell medium in the first and/or second gas permeable container is unfiltered.
  • particulate serum components present in some cell medium supplements e.g., AB serum
  • the use of unfiltered cell medium may, advantageously, simplify the procedures necessary to expand the number of cells.
  • the cell medium in the first and/or second gas permeable container lacks beta-mercaptoethanol (BME).
  • BME beta-mercaptoethanol
  • the duration of the method comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining TIL from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells may be about 28 to about 42 days, e.g., about 28 days.
  • the method comprises administering the expanded TIL to the mammal.
  • the TIL can be administered by any suitable route as known in the art.
  • the TIL are administered as an intra-arterial or intravenous infusion, which preferably lasts about 30 to about 60 minutes.
  • routes of administration include intraperitoneal, intrathecal and intralymphatic.
  • any suitable dose of TIL can be administered.
  • from about 1.2 ⁇ 10 10 to about 4.3 ⁇ 10 10 TIL are administered.
  • macrophages, monocytes, and natural killer (NK) cells may also be obtained from the tumor tissue sample, cultured, and expanded as described herein for TIL. Accordingly, the method may also comprise administering macrophages, monocytes, and natural killer (NK) cells to the mammal.
  • the inventive methods may also be effective for expanding NK cells.
  • a T-cell growth factor that promotes the growth and activation of the TIL is administered to the mammal either concomitantly with the TIL or subsequently to the TIL.
  • the T-cell growth factor can be any suitable growth factor that promotes the growth and activation of the TIL.
  • suitable T-cell growth factors include interleukin (IL)-2, IL-7, IL-15, and IL-12, which can be used alone or in various combinations, such as IL-2 and IL-7, IL-2 and IL-15, IL-7 and IL-15, IL-2, IL-7 and IL-15, IL-12 and IL-7, IL-12 and IL-15, or IL-12 and IL-2.
  • IL-2 is a preferred T-cell growth factor.
  • the TIL are modified to express a T-cell growth factor that promotes the growth and activation of the TIL.
  • Suitable T-cell growth factors include, for example, any of those described above. Suitable methods of modification are known in the art. See, for instance, Sambrook et al., Molecular Cloning: A Laboratory Manual, 3 rd ed., Cold Spring Harbor Press, Cold Spring Harbor, N.Y. 2001; and Ausubel et al., Current Protocols in Molecular Biology , Greene Publishing Associates and John Wiley & Sons, NY, 1994. Desirably, modified TIL express the T-cell growth factor at high levels.
  • T-cell growth factor coding sequences such as that of IL-12, are readily available in the art, as are promoters, the operable linkage of which to a T-cell growth factor coding sequence promote high-level expression.
  • the TIL may be modified to express IL-12 as described in World Intellectual Property Organization Patent Application Publication No. WO 2010/126766, which is incorporated herein by reference.
  • two cytokines are more effective than a single cytokine, and three cytokines, e.g., IL-2, IL-7 and IL-15, are more effective than any two cytokines.
  • IL-15 enhances a tumor-specific CD8 + T-cell response.
  • the administration of IL-15-cultured cells with IL-2 can be particularly efficacious.
  • TIL modified to express IL-12 may be administered with IL-2 as a bolus injection.
  • the T-cell growth factor can be administered by any suitable route. If more than one T-cell growth factor is administered, they can be administered simultaneously or sequentially, in any order, and by the same route or different routes.
  • the T-cell growth factor, such as IL-2 is administered intravenously as a bolus injection.
  • the dosage of the T-cell growth factor, such as IL-2 is what is considered by those of ordinary skill in the art to be high.
  • a dose of about 720,000 IU/kg of IL-2 is administered three times daily until tolerance, particularly when the cancer is melanoma.
  • about 5 to about 15 doses of IL-2 are administered, with an average of around 8 doses.
  • TIL can recognize any of the unique antigens produced as a result of the estimated 10,000 genetic mutations encoded by each tumor cell genome.
  • the antigen need not be unique.
  • TIL can recognize one or more antigens of a cancer, including an antigenic portion of one or more antigens, such as an epitope, or a cell of the cancer.
  • An “antigen of a cancer” and an “antigen of the cancer” are intended to encompass all of the aforementioned antigens.
  • the cancer is melanoma, such as metastatic melanoma
  • the TIL recognize MART-1 (such as MART-1:26-35 (27L)), gp100 (such as gp100:209-217 (210M)), or a “unique” or patient-specific antigen derived from a tumor-encoded mutation.
  • MART-1 such as MART-1:26-35 (27L)
  • gp100 such as gp100:209-217 (210M)
  • a “unique” or patient-specific antigen derived from a tumor-encoded mutation can include, but are not limited to, tyrosinase, tyrosinase related protein (TRP)1, TRP2, and MAGE.
  • TIL can also recognize antigens such as, for example, NY-ESO-1, telomerase, p53, HER2/neu, carcinoembryonic antigen, or prostate-specific antigen, for treatment of lung carcinoma, breast cancer, colon cancer, prostate cancer, and the like.
  • antigens such as, for example, NY-ESO-1, telomerase, p53, HER2/neu, carcinoembryonic antigen, or prostate-specific antigen, for treatment of lung carcinoma, breast cancer, colon cancer, prostate cancer, and the like.
  • the TIL are modified to express a T cell receptor (TCR) having antigenic specificity for a cancer antigen, e.g., any of the cancer antigens described herein.
  • TCRs include, for example, those with antigenic specificity for a melanoma antigen, e.g., gp100 or MART-1. Suitable methods of modification are known in the art. See, for instance, Sambrook and Ausubel, supra.
  • the TIL may be transduced to express a T cell receptor (TCR) having antigenic specificity for a cancer antigen using transduction techniques described in Morgan et al., Science 314(5796):126-9 (2006) and Johnson et al. Blood 114:535-46 (2009).
  • the cancer can be any cancer, including any of acute lymphocytic cancer, acute myeloid leukemia, alveolar rhabdomyosarcoma, bone cancer, brain cancer, breast cancer, cancer of the anus, anal canal, or anorectum, cancer of the eye, cancer of the intrahepatic bile duct, cancer of the joints, cancer of the neck, gallbladder, or pleura, cancer of the nose, nasal cavity, or middle ear, cancer of the oral cavity, cancer of the vulva, chronic lymphocytic leukemia, chronic myeloid cancer, colon cancer, esophageal cancer, cervical cancer, gastrointestinal carcinoid tumor, glioma, Hodgkin lymphoma, hypopharynx cancer, kidney cancer, larynx cancer, liver cancer, lung cancer, malignant mesothelioma, melanoma, multiple myeloma, nasopharynx cancer, non-Hodgkin lymphoma, ovarian cancer
  • the term “mammal” refers to any mammal, including, but not limited to, mammals of the order Rodentia, such as mice and hamsters, and mammals of the order Logomorpha, such as rabbits. It is preferred that the mammals are from the order Carnivora, including Felines (cats) and Canines (dogs). It is more preferred that the mammals are from the order Artiodactyla, including Bovines (cows) and Swines (pigs) or of the order Perssodactyla, including Equines (horses). It is most preferred that the mammals are of the order Primates, Ceboids, or Simoids (monkeys) or of the order Anthropoids (humans and apes). An especially preferred mammal is the human.
  • Promoting regression of cancer in a mammal may comprise treating or preventing cancer in the mammal.
  • the terms “treat,” “prevent,” and “regression,” as well as words stemming therefrom, as used herein, does not necessarily imply 100% or complete regression. Rather, there are varying degrees of treatment, prevention, and regression of which one of ordinary skill in the art recognizes as having a potential benefit or therapeutic effect.
  • the inventive methods can provide any amount of any level of treatment, prevention, or regression of cancer in a mammal.
  • the treatment, prevention, or regression provided by the inventive method can include treatment, prevention, or regression of one or more conditions or symptoms of the disease, e.g., cancer.
  • “treatment,” “prevention,” and “regression” can encompass delaying the onset of the disease, or a symptom or condition thereof.
  • Another embodiment provides a method of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining TIL from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells.
  • the method comprises obtaining a tumor tissue sample from the mammal.
  • the tumor tissue sample may be obtained as described herein with respect to any embodiments of the invention.
  • the method comprises culturing the tumor tissue sample in a first gas permeable container containing cell medium therein.
  • the tumor tissue sample may be cultured in a first gas permeable container as described herein with respect to any embodiments of the invention.
  • the method comprises obtaining TIL from the tumor tissue sample.
  • the TIL may be obtained from the tumor tissue sample as described herein with respect to any embodiments of the invention.
  • the method comprises expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells.
  • the number of TIL may be expanded as described herein with respect to any embodiments of the invention.
  • Still another embodiment of the invention provides a method of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy comprising obtaining a tumor tissue sample from the mammal; obtaining TIL from the tumor tissue sample; expanding the number of TIL in a gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells.
  • Obtaining a tumor tissue sample from the mammal, obtaining TIL from the tumor tissue sample, and expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells may be carried out as described herein with respect to any embodiments of the invention.
  • the method may further comprise culturing the tumor tissue by any suitable method that facilitates the obtaining of TIL from the tumor tissue sample.
  • culturing the tumor tissue may comprise establishing multiple independent cultures, e.g., microcultures.
  • culturing the tumor tissue may comprise culturing tumor fragments in plates, e.g., 24-well plates.
  • the tumor tissue is cultured without a gas permeable container.
  • the method further comprises selecting TIL capable of lysing cancer cells while in other embodiments, the method does not include selecting TIL capable of lysing cancer cells.
  • TIL capable of lysing cancer cells may be selected by identifying TILs having any suitable trait associated with the lysis of cancer cells and/or the regression of cancer.
  • Exemplary suitable TIL traits that may serve as the basis for selecting TILs may include any one or more of IFN- ⁇ release upon co-culture with autologous tumor cells; cell surface expression of one or more of CD8, CD27, and CD28; and telomere length.
  • telomere lengths are associated with positive objective clinical responses in patients and persistence of the cells in vivo.
  • the trait is IFN- ⁇ release upon co-culture with autologous tumor cells.
  • selected TIL release about 200 pg/ml or more of IFN- ⁇ upon co-culture with tumor cells.
  • selecting TIL capable of lysing cancer cells comprises testing individual cultures for presence of the trait and identifying TIL possessing the trait. Methods of testing cultures for the presence of any one or more of IFN- ⁇ release upon co-culture with autologous tumor cells; cell surface expression of one or more of CD8, CD27, and CD28; and telomere length (longer telomeres being associated with regression of cancer) are known in the art.
  • any number of cultures may be selected. For example, one, two, three, four, five, or more cultures may be selected. In embodiments in which two or more cultures are selected, the selected cultures may be combined and the number of TIL expanded in one (or more) gas permeable containers. Preferably, however, in embodiments in which two or more cultures are selected, each selected culture is separately expanded in separate gas permeable containers. Without being bound to a particular theory, it is believed that expanding multiple selected cultures separately advantageously increases lymphocyte diversity for patient treatment.
  • the method may further comprise expanding the number of TIL in an identified culture in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells as described herein with respect to any embodiments of the invention.
  • Another embodiment of the invention provides a method of promoting regression of cancer in a mammal comprising obtaining a tumor tissue sample from the mammal; obtaining TIL from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and administering the expanded number of TIL to the mammal.
  • Obtaining a tumor tissue sample from the mammal, obtaining TIL from the tumor tissue sample, expanding the number of TIL in a gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells, and administering the expanded number of TIL to the mammal may be carried out as described herein with respect to any embodiments of the invention.
  • the method further comprises selecting TIL capable of lysing cancer cells. The TIL may be selected as described herein with respect to any embodiments of the invention.
  • TIL tumor fragments
  • RPMI Roswell Park Memorial Institute
  • the solution was then incubated for 30 minutes at 37° C. in 5% CO 2 and was then mechanically disrupted again approximately 1 minute. After being incubated again for 30 minutes at 37° C. in 5% CO 2 , the tumor was mechanically disrupted a third time for approximately one minute. If after the third mechanical disruption, large pieces of tissue were present, one or two additional mechanical dissociations were applied to the sample, with or without 30 additional minutes of incubation at 37° C. in 5% CO 2 . At the end of the final incubation, if the cell suspension contained a large number of red blood cells or dead cells, a density gradient separation using FICOLL branched hydrophilic polysaccharide (GE Healthcare, Smyrna, Ga.) was preformed to remove these cells.
  • FICOLL branched hydrophilic polysaccharide GE Healthcare, Smyrna, Ga.
  • TIL growth from digests and fragments were initiated in either gas permeable flasks with a 40 mL volume and a 10 cm 2 gas-permeable silicon bottom (G-Rex10, Wilson Wolf Manufacturing, New Brighton, Minn., USA) or 24-well plates (Corning Corning, N.Y.).
  • G-Rex10 Wilson Wolf Manufacturing, New Brighton, Minn., USA
  • 24-well plates Corning Corning, N.Y.
  • each well was seeded with 1 ⁇ 10 6 tumor digest cells or one tumor fragment approximately 1 to 8 mm 3 in size in 2 mL of CM with IL-2 (6000 IU/mL, Chiron Corp., Emeryville, Calif.).
  • CM included RPMI 1640 with glutamine, supplemented with 10% AB serum, 25 mM Hepes and 10 ⁇ g/ml gentamicin.
  • G-Rex10 flasks When cultures were initiated in G-Rex10 flasks, each flask was loaded with 10 to 40 ⁇ 10 6 viable tumor digest cells or 5 to 30 tumor fragments in 10 to 40 ml of CM with IL-2.
  • Both the G-Rex10 and 24-well plates were incubated in a humidified incubator at 37° C. in 5% CO 2 and five days after culture initiation, half the media was removed and replaced with fresh CM and IL-2 and after day 5, half the media was changed every 2 to 3 days.
  • TIL REP of TIL was performed using T-175 flasks and gas permeable bags as previously described (Tran et al., J. Immunother. 31(8):742-51 (2008); Dudley et al., J. Immunother. 26(4):332-42 (2003)) or gas permeable cultureware (G-Rex flasks).
  • TIL REP in T-175 flasks 1 ⁇ 10 6 TIL suspended in 150 ml of media was added to each T-175 flask.
  • the TIL were cultured with irradiated (50 Gy) allogeneic peripheral blood mononuclear cells (PBMC) as “feeder” cells at a ratio of 1 TIL to 100 feeder cells and the cells were cultured in a 1 to 1 mixture of CM and AIM-V medium, supplemented with 3000 IU per mL of IL-2 and 30 ng per ml of anti-CD3.
  • PBMC peripheral blood mononuclear cells
  • the T-175 flasks were incubated at 37° C. in 5% CO 2 . Half the media was exchanged on day 5 using 50/50 medium with 3000 IU per mL of IL-2.
  • TIL REP for TIL REP in 500 mL capacity gas permeable flasks with 100 cm 2 gas-permeable silicon bottoms (G-Rex100, commercially available from Wilson Wolf Manufacturing Corporation, New Brighton, Minn., USA), 5 ⁇ 10 6 or 10 ⁇ 10 6 TIL were cultured with irradiated allogeneic PBMC at a ratio of 1 to 100 in 400 mL of 50/50 medium, supplemented with 5% human AB serum, 3000 IU per mL of IL-2 and 30 ng per ml of anti-CD3. The G-Rex100 flasks were incubated at 37° C. in 5% CO 2 .
  • CD3, CD4, CD8 and CD56 were measured by flow cytometry with antibodies from BD Biosciences (BD Biosciences, San Jose, Calif.) using a FACSCantoTM flow cytometer (BD Biosciences). The cells were counted manually using a disposable hemacytometer and viability was assessed using trypan blue staining.
  • TIL were evaluated for interferon-gamma (IFN- ⁇ ) secretion in response to stimulation either with OKT3 antibody or co-culture with autologous tumor digest.
  • OKT3 stimulation TIL were washed extensively, and duplicate wells were prepared with 1 ⁇ 10 5 cells in 0.2 ml CM in 96 well flat-bottom plates pre-coated with 0.1 or 1.0 ⁇ g/mL of OKT-3 antibody diluted in PBS. After overnight incubation, the supernatants were harvested and IFN- ⁇ in the supernatant was measured by ELISA (Pierce/Endogen, Woburn, Mass.).
  • ELISA Westernce/Endogen, Woburn, Mass.
  • TIL cells were placed into a 96-well plate with autologous tumor cells. After a 24 hour incubation, supernatants were harvested and IFN- ⁇ release was quantified by ELISA.
  • TIL cultured in gas-permeable containers is better than, or at least comparable to, that in a 24-well plate.
  • TIL from tumors using gas permeable flasks with a 40 mL capacity and 10 cm 2 gas permeable silicone bottom (G-Rex10, Wilson Wolf Manufacturing Corporation, New Brighton, Minn., USA (providing about 10 cm 2 of surface area for growth of the TIL)) or 24-well plates (Corning Corning, N.Y.) was compared.
  • a total of 14 melanoma samples were tested, including 9 freshly prepared tumor digests (Table 1A) and 5 thawed samples from previously frozen tumor digests (Table 1B).
  • TIL from frozen tumor from patient 2653 were not able to be cultured in either the G-Rex10 or 24-well plates. Except for one fresh sample (#3522), the ratio of harvested TIL to initially seeded cells at day 17 to 29 was similar to or better in the G-Rex10 flasks than in the 24-well plate (Table 1A and 1B).
  • IFN- ⁇ production by TIL cultured in G-Rex10 flasks was also compared with that of TIL cultured in 24-well plates. IFN- ⁇ production following stimulation with autologous tumor by TIL from 4 patients cultured in both types of vessels was similar (Table 1C)
  • This example demonstrates that the culture of TIL from tumor fragments in gas permeable flasks produces a greater number of TIL as compared to culture in 24-well plates after 7 to 13 days.
  • TIL tumor fragments in G-Rex10 flasks or 24-well plates was next compared. For each tumor sample, fragments approximately 1 to 8 mm 3 in size were seeded into 24-well plates at 1 piece per well and into G-Rex10 flasks at 5, 10, 20, or 30 pieces per flask. The growth of TIL from 2 lymph nodes and 1 liver metastasis was assessed (Table 2). TIL could be grown from tumor fragments in both gas-permeable flasks and 24-well plates, but after 7 to 13 days greater quantities of TIL were obtained from the G-Rex10 flasks than the wells (Table 2).
  • TIL tumor fragments from all 11 samples in both the G-Rex10 flasks and 24-well plates, but after 7 to 23 days in culture greater quantities of TIL were obtained from the G-Rex10 flasks.
  • the head-to-head comparison of culturing 10 fragments in the two types of vessels showed that TIL yields from G-Rex10 flasks were consistently higher than those from 24-well plate ( FIG. 1A ).
  • TIL obtained per tumor fragment decreased as the number of pieces added to each G-Rex10 flask increased ( FIG. 1B ), however, total TIL yield was higher as more fragments were cultured in the G-Rex10 flasks until 20 or more tumor fragments were cultured in each G-Rex10 flask ( FIG. 1C ).
  • the viability of TIL obtained from G-Rex10 flasks was similar to that of TIL obtained from 24-well plates (96.6 ⁇ 0.6% vs 95.3 ⁇ 0.8%) as was the proportion of TIL expressing CD3 and CD8 (67.8 ⁇ 7.2% vs 63.3 ⁇ 7.7%).
  • TIL were also obtained from 3 of the 11 samples by the culture of mechanically dissociated samples in G-Rex10 flasks, but greater yields were obtained using tumor fragments as the starting material.
  • This example demonstrates the kinetics of TIL growth in gas-permeable flasks.
  • TIL from one patient were cultured in G-Rex100 flasks seeded at a density of 5 ⁇ 10 6 and 10 ⁇ 10 6 cells per flask. The cells were counted daily after day 6. On Day 6 the number of cells in the G-Rex100 flask seeded at 5 ⁇ 10 6 cells was 255 ⁇ 10 6 cells and at 10 ⁇ 10 6 cells was 300 ⁇ 10 6 cells. The quantity of TIL in G-Rex100 flasks seeded at each cell density increased steadily until day 9, but there was little increase in cell counts between days 9 and 10.
  • TIL After 10 days 906 ⁇ 10 6 cells were harvested from flasks seeded with 5 ⁇ 10 6 TIL and 1,050 ⁇ 10 6 cells from flasks seeded with 10 ⁇ 10 6 TIL. Although TIL expanded well for 9 days, in order to keep the G-Rex100 flask expansion process similar to REP in T-flasks and gas-permeable bags where TIL are transferred from T-flasks to bags on day 7, further studies focused on TIL expansion in the G-Rex100 flasks for 7 days.
  • This example demonstrates that a 7-day culture of TIL in a gas permeable container seeded with 10 ⁇ 10 6 cells does not produce a significantly greater number of cells than a gas permeable container seeded with 5 ⁇ 10 6 cells.
  • TIL rapid expansion protocol has traditionally been performed in T-175 flasks.
  • the expansion of TIL in T-175 flasks was compared to expansion in G-Rex100 flasks (providing about 100 cm 2 of surface area for growth of the TIL).
  • the expansion of TIL from 4 patients over 7 days in G-Rex100 flasks seeded with 5 ⁇ 10 6 and 10 ⁇ 10 6 cells was compared with TIL expansion in T-175 flasks (Table 3). T-175 flasks were seeded with 1 ⁇ 10 6 cells.
  • This example demonstrates that a similar number of cells can be produced in a 500 mL gas permeable container as compared to a 2000 mL gas permeable container.
  • TIL REP by serial culture was tested in G-Rex100L, another type of gas-permeable flask that is commercially available for large scale cell expansion (Wilson Wolf Manufacturing Corporation, New Brighton, Minn., USA).
  • G-Rex100L has the same gas permeable surface area on the silicone bottom of the flask as the G-Rex100 (providing about 100 cm 2 of surface area for growth of the TIL), but the G-Rex100L is taller.
  • the media capacity of the G-Rex100L flask is approximately 2000 ml compared to approximately 500 mL for the G-Rex100.
  • TIL expansion was compared in these two types of flasks.
  • TIL were initially seeded at a density of 5 ⁇ 10 6 cells for both the G-Rex100 and G-Rex100L flasks, and were cultured for 7 days as described in Example 3. After 7 days the cells from the G-Rex100 flask were split into 3 equal parts, and seeded into 3 G-Rex100L flasks. The cells from the G-Rex100L flask were split into two equal parts, seeded into 2 G-Rex100L flasks. The TIL were cultured for an additional 7 days in the G-Rex100 and G-Rex100L flasks.
  • TIL TIL-Rex100
  • G-Rex100L flasks The expansion of TIL from two patients was compared in the G-Rex100 and G-Rex100L flasks. Both patients' TIL growth slowed after 13 or 14 days.
  • This example demonstrates the consistency of serial TIL expansion using gas permeable containers and a “full scale” expansion of TIL using gas permeable containers.
  • TIL serial TIL expansion in G-Rex100 flasks using cells from 14 patients was tested. Initially, 5 ⁇ 10 6 TIL were seeded into a G-Rex100 flask and the cells were cultured for 7 days. They were then split into 3 equal parts, seeded into 3 G-Rex100 flasks. After 14 days in culture, 8.60 ⁇ 10 9 ⁇ 2.80 ⁇ 10 9 TIL with a range of 2.24 ⁇ 10 9 to 12.8 ⁇ 10 9 were produced. The number of TIL produced after 14 days was similar for 12 patients, but lower for two others. When the 2 patients with the lowest overall TIL expansion were excluded, the mean quantity of TIL produced was 9.55 ⁇ 10 9 cells per original G-Rex100 flask. The mean cell concentration in G-Rex100 flasks at the end of the culture was 7.95 ⁇ 10 6 cells per mL.
  • TIL produced by G-Rex100 REP and T-175 flask/bag REP was compared.
  • TIL samples produced by both REP methods using the same tumor samples from 4 patients were tested.
  • Following stimulation by anti-CD3 IFN- ⁇ production by TIL expanded in G-Rex100 flasks was similar to that of TIL expanded in T-175 flasks and bags (Table 4A).
  • G-Rex100 REP 15 ⁇ 10 6 TIL from one patient were divided among three G-Rex100 flasks, A, B and C. After 7 days in culture the TIL in each flask were split into 3 equal parts, seeded into 3 G-Rex100 flasks and cultured for an additional 7 days.
  • the mean number of TIL harvested from each of the 3 G-Rex100 flasks used for initial expansion was 875 ⁇ 10 6 ⁇ 30.8 ⁇ 10 6 and ranged from 849 ⁇ 10 6 to 909 ⁇ 10 6 TIL and the mean number harvested from each of the 9 G-Rex100 flasks used for the secondary expansion was 2.63 ⁇ 0.09 ⁇ 10 9 and ranged for 2.55 ⁇ 10 9 to 2.70 ⁇ 10 9 TIL (Table 5).
  • the total TIL yield was 23.6 ⁇ 10 9 and 21.0 ⁇ 10 9 remained after washing the cells.
  • the viability of the cells was 96% and 69% of the cells expressed CD3 and CD8.
  • IFN- ⁇ secretion was also tested using Enzyme-linked immunosorbent assay (ELISA).
  • ELISA Enzyme-linked immunosorbent assay
  • This example demonstrates the rapid expansion of TIL using one 5000 mL gas permeable container.
  • One method involved an initial 7-day expansion in 2 G-Rex100 flasks, each seeded with 5 ⁇ 10 6 TIL, followed by another expansion of the harvested TIL in a single GP5000 vessel.
  • the other method involved a single 14-day expansion of 10 ⁇ 10 6 TIL in a GP5000 vessel.
  • TIL yield of the two REP methods were similar for both donors. Approximately 25 ⁇ 10 9 TIL were harvested from patient 3524 and approximately 20 ⁇ 10 9 from patient 3560. The cell viability for all four REPs was >96% and >92% of patient 3524 cells expressed CD8 and >35% of patient 3560 cells expressed CD8.
  • This example demonstrates a clinical TIL production process.
  • TIL production using tumor fragments from 3 patients was next tested by initially culturing TIL in G-Rex10 flasks followed by REP in G-Rex100 flasks.
  • 6 G-Rex10 flasks were seeded with 5 tumor fragments and after 14 to 15 days 5 ⁇ 10 6 TIL from each G-Rex10 flask were seeded into one G-Rex100 flask.
  • 7 days TIL from each G-Rex100 flask were split into 3 G-Rex100 flasks and after an additional 7 days in culture TIL were harvested from the 18 G-Rex100 flasks.
  • TIL were harvested from the 18 G-Rex100 flasks.
  • 3613 and 3618 enough TIL could be harvested from each of the 6 G-Rex10 flasks for TIL REP in a G-Rex100 flask.
  • the quantity of TIL harvested from each of the G-Rex10 flasks ranged from 47.5 to 97.8 ⁇ 10 6 cells for patient 3613 and 24.6 to 64.2 ⁇ 10 6 for patient 3618 (Table 6A).
  • sufficient quantities of TIL were obtained from 4 of the 6 G-Rex10 flasks.
  • the quantity harvested from these 4 flasks ranged from 59.7 to 140 ⁇ 10 6 cells (Table 6A).
  • 5 ⁇ 10 6 TIL from each of the 6 G-Rex10 flasks was seeded into a G-Rex100 flask.
  • G-Rex100 flasks can produce sufficient quantities of TIL for clinical therapy using TIL initially cultured from tumor fragments in G-Rex10 flasks.
  • the same G-Rex100 REP protocol was also successful in expanding TIL that were initially cultured from tumor fragments in 24-well plates. There were no significant differences in fold expansion using either TIL initially cultured from tumor fragments in 24-well plates or G-Rex10 flasks.
  • This example demonstrates that expanding TIL in gas permeable containers uses a lower number of containers, lower number of feeder cells, and lower amount of medium as compared to methods in which the TIL are expanded in non-gas permeable containers.
  • TIL are expanded as described above using gas permeable containers (G-Rex100 and GP5000) and in non-gas permeable containers (bags and T 175 flask).
  • G-Rex100 and GP5000 gas permeable containers
  • bags and T 175 flask bags and T 175 flask
  • TIL 4 ⁇ 10 6 ) were cultured in filtered or unfiltered complete medium (CM) (50 mL) (RPMI 1640 with glutamine, supplemented with 10% AB serum, 25 mM Hepes and 10 ⁇ g/ml gentamicin) in four wells. On day 7/8, fold increase, viability, and % CD3+CD8+ were measured. The results are shown in Table 7.
  • This example demonstrates that culturing TIL in cell medium that lacks beta-mercaptoethanol (BME) has little or no detrimental effects on TIL growth or potency.
  • BME beta-mercaptoethanol
  • TIL were cultured in complete medium (CM) (50 mL) with or without BME. After 2-3 weeks, population increase, viability, and % CD3+CD8+ were measured. The results are shown in Table 8. ⁇ 10 7
  • the performance of the TIL cultured in the medium without BME was similar to that of the TIL cultured in the medium with BME.
  • TIL Effector
  • TIL Effector cells (1 ⁇ 10 5 ) are co-cultured with target (antigen-presenting tumor cells) cells (1 ⁇ 10 5 ), with AK1700 used as a negative control and DM5 A2 used as a positive control.
  • IFN-gamma secretion is measured by ELISA. There was no significant difference in IFN-gamma secretion for the TIL cultured in medium without BME as compared to TIL cultured in medium with BME. Thus, the absence of BME from the medium has little or no detrimental effects on TIL cell growth or potency.
  • This example demonstrates that feeding the TIL no more frequently than every third or fourth day during expansion of the number of TIL in a gas permeable container has little or no detrimental effects on TIL growth.
  • TIL were rapidly expanded in a 500 mL gas permeable container (G-Rex100) as described above and fed as described in Table 9. At the end of 14 days, fold expansion, viability, and composition were measured.
  • TIL potency of the TIL is measured and compared for TIL cultured and fed every third or fourth day as compared to TIL fed every other day. Effector cells (1 ⁇ 10 5 ) are co-cultured with target cells (1 ⁇ 10 5 ), with AK1700 used as a negative control and DM5 A2 used as a positive control. IFN-gamma secretion is measured by ELISA. There was no significant difference in IFN-gamma secretion for the TIL fed every third or fourth day as compared to TIL fed every other day. Thus, the reduction in feeding frequency has little or no detrimental effects on TIL potency.
  • This example demonstrates that using no more than one type of cell culture medium for expanding the number of TIL has little or no detrimental effects on TIL growth.
  • TIL were rapidly expanded as described above using no more than one type of cell culture medium or two types of cell culture medium as set forth in Table 11.
  • TIL Potency of the TIL is measured and compared for TIL expanded using no more than one type of medium and TIL expanded using two types of medium. Effector cells (1 ⁇ 10 5 ) are co-cultured with target cells (1 ⁇ 10 5 ), with AK1700 used as a negative control and DM5 A2 used as a positive control. IFN-gamma secretion is measured by ELISA. There was no significant difference in IFN-gamma secretion for TIL expanded using no more than one type of cell medium as compared to TIL expanded using two types of cell medium.
  • This example demonstrates that expanding the number of TIL using a higher ratio of feeders provides a higher number of TIL.
  • TIL 5 ⁇ 10 6 ) from two tumor samples were expanded as described above using allogeneic feeder cells at a TIL:Feeder cell ratio of 1:100, 1:50, or 1:25. Cells were counted on days 7, 11, and 14. Viability and cellular composition were evaluated on day 14.
  • TIL cultured in a gas permeable container have the same or better potency as compared to TIL cultured in non-gas permeable, 24 well plates.
  • TIL are cultured in a gas permeable container (40 mL, G-Rex10) or in a non-gas permeable, 24-well plate. Effector cells (1 ⁇ 10 5 ) are co-cultured with target cells (1 ⁇ 10 5 ), with AK1700 used as a negative control and DM5 A2 used as a positive control. IFN-gamma secretion is measured by ELISA. The results are shown in Table 13.
  • This example demonstrates the treatment of melanoma using TIL prepared by initially culturing the TIL in gas permeable flasks and then rapidly expanding the number of TIL in gas permeable flasks.
  • Tumor tissue samples were obtained from seven melanoma patients. The tumor tissue samples were cultured in G-Rex10 flasks. TIL were obtained from the cultured tumor tissue samples. The numbers of TIL were expanded in G-Rex100 flasks. The expanded cells were administered to the patients.
  • This example demonstrates the treatment of melanoma using TIL prepared by expanding the number of selected TIL in gas permeable flasks.
  • Compete medium (2 ml) (supplemented with 6000 IU/ml IL-2) was added to the wells in the top row of each 24-well plate. A single fragment of tumor was added to each media-containing well.
  • TIL were obtained from the tumor tissue samples and cultured as follows. Fragments were incubated in multiwell plates in a humidified incubator at 37° C., with 5% CO 2 in air for 5 days without disturbance. After 5 days, the TIL cultures in plates were monitored for growth by viewing with an inverted light microscope. At this point TIL and other cell types have extravasated from the fragment and/or propagated in the wells. Half of the CM in plates was replaced with fresh CM containing IL-2 (6000 IU/ml). Media (1 ml) was aspirated, taking care not to disturb the cells on the bottom of the well, and replaced with 1 ml of fresh medium containing IL-2 (6000 CU/ml).
  • the plates were monitored for TIL growth. When TIL expansion was evident, a sample from the well was counted to quantify cell concentration. When the culture exceeded 1 ⁇ 10 6 lymphocytes/ml or became nearly confluent then the well was split 1:2. Splitting was accomplished by mixing gently with a transfer pipette and transferring 1 ml of culture to a new well, then adding 1 ml of CM containing IL-2 (6000 IU/ml) to each daughter well. Fragment cultures that showed growth, up to 24 in total, were split in to 2 wells. The first 12 fragment cultures that required a second split in to 4 wells were maintained. The remaining fragment cultures were frozen as a pool 1 (PF1).
  • PF1 pool 1
  • the cultures were screened for specificity by co-culturing 100 ⁇ l of TIL with media only, autologous fresh tumor cells, or autologous fresh tumor cells and MHC Class I antibody, and IFN- ⁇ release was measured. Reactive cultures were selected for expansion.
  • TIL from the selected cultures that released 200 pg/ml or more of IFN- ⁇
  • the expanded cells were administered to the patients.
US13/424,646 2011-03-22 2012-03-20 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers Abandoned US20120244133A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US13/424,646 US20120244133A1 (en) 2011-03-22 2012-03-20 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers
US15/375,289 US20170152478A1 (en) 2011-03-22 2016-12-12 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers
US16/211,859 US11401503B2 (en) 2011-03-22 2018-12-06 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161466200P 2011-03-22 2011-03-22
US13/424,646 US20120244133A1 (en) 2011-03-22 2012-03-20 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/375,289 Continuation US20170152478A1 (en) 2011-03-22 2016-12-12 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers

Publications (1)

Publication Number Publication Date
US20120244133A1 true US20120244133A1 (en) 2012-09-27

Family

ID=45937598

Family Applications (3)

Application Number Title Priority Date Filing Date
US13/424,646 Abandoned US20120244133A1 (en) 2011-03-22 2012-03-20 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers
US15/375,289 Abandoned US20170152478A1 (en) 2011-03-22 2016-12-12 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers
US16/211,859 Active 2032-04-19 US11401503B2 (en) 2011-03-22 2018-12-06 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers

Family Applications After (2)

Application Number Title Priority Date Filing Date
US15/375,289 Abandoned US20170152478A1 (en) 2011-03-22 2016-12-12 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers
US16/211,859 Active 2032-04-19 US11401503B2 (en) 2011-03-22 2018-12-06 Methods of growing tumor infiltrating lymphocytes in gas-permeable containers

Country Status (2)

Country Link
US (3) US20120244133A1 (fr)
WO (1) WO2012129201A1 (fr)

Cited By (183)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014133567A1 (fr) 2013-03-01 2014-09-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations enrichies de lymphocytes t réactifs à une tumeur à partir d'une tumeur
WO2014133568A1 (fr) 2013-03-01 2014-09-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations enrichies de lymphocytes t réactifs à une tumeur à partir de sang périphérique
WO2015009604A1 (fr) 2013-07-15 2015-01-22 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de préparation de cellules t antigéniques anti-papillomavirus humain
WO2015009606A1 (fr) 2013-07-15 2015-01-22 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t anti-papillomavirus humain 16 e6
WO2015184228A1 (fr) 2014-05-29 2015-12-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t anti-papillomavirus humain 16 e7
WO2016053339A1 (fr) 2014-10-02 2016-04-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Méthodes d'isolation de cellules t présentant une spécificité antigénique pour une mutation spécifique d'un cancer
WO2016053338A1 (fr) 2014-10-02 2016-04-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de récepteurs des lymphocytes t présentant une spécificité antigénique pour une mutation spécifique du cancer
WO2016077525A2 (fr) 2014-11-14 2016-05-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t anti-thyroblobuline humaine
WO2016085904A1 (fr) 2014-11-26 2016-06-02 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t kras anti-mutation
WO2016100977A1 (fr) 2014-12-19 2016-06-23 The Broad Institute Inc. Procédés pour le profilage du répertoire de récepteurs de cellules t
WO2016138182A1 (fr) * 2015-02-24 2016-09-01 Nodality, Inc. Méthodes et compositions d'immunomodulation
WO2016179006A1 (fr) 2015-05-01 2016-11-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de cellules t et de récepteurs des cellules t ayant une spécificité antigénique pour une mutation spécifique au cancer du sang périphérique
WO2017035251A1 (fr) 2015-08-25 2017-03-02 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Lymphocytes t modifiés pour surexprimer la c-myb
WO2017048593A1 (fr) 2015-09-15 2017-03-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t reconnaissant les gènes kras mutés limités en hla-cw8
WO2017066122A1 (fr) 2015-10-15 2017-04-20 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs antigéniques chimériques anti-cd30
WO2017070042A1 (fr) 2015-10-20 2017-04-27 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations de lymphocytes t à l'aide d'inhibiteurs d'akt
WO2017069958A2 (fr) 2015-10-09 2017-04-27 The Brigham And Women's Hospital, Inc. Modulation de nouvelles cibles de points de contrôle immunitaires
WO2017075451A1 (fr) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions et procédés d'évaluation et de modulation des réponses immunitaires par détection et ciblage de pou2af1
WO2017075478A2 (fr) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions et méthodes d'évaluation et de modulation des réponses immunitaires à l'aide de signatures génétiques de cellules immunitaires
WO2017075465A1 (fr) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions et procédés d'évaluation et de modulation des réponses immunitaires par détection et ciblage de gata3
WO2017079113A1 (fr) 2015-11-02 2017-05-11 The United States Of America, As Represented By The Secretary, Department Of Healh And Human Services Procédés de production de populations de lymphocytes t à l'aide d'inhibiteurs de protéines contenant un domaine prolyl hydroxylase
WO2017087708A1 (fr) 2015-11-19 2017-05-26 The Brigham And Women's Hospital, Inc. Hétérodimères dans l'immunité de l'interleukine 12b (p40) de type antigène lymphocytaire cd5 (cd5l)
WO2017139199A1 (fr) 2016-02-10 2017-08-17 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Arginase inductible
WO2017178572A1 (fr) 2016-04-13 2017-10-19 Vivia Biotech, S.L Cellules t destructrices de cellules tumorales et leurs utilisations
WO2017189254A1 (fr) 2016-04-26 2017-11-02 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t anti-kk-lc-1
CN107502589A (zh) * 2017-08-04 2017-12-22 北京世纪劲得生物技术有限公司 一种肿瘤浸润淋巴细胞与单个核细胞共培养方法
WO2018026691A1 (fr) 2016-08-02 2018-02-08 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs des lymphocytes t anti-kras-g12d
WO2018049025A2 (fr) 2016-09-07 2018-03-15 The Broad Institute Inc. Compositions et procédés pour évaluer et moduler des réponses immunitaires
WO2018057769A1 (fr) 2016-09-22 2018-03-29 Corning Incorporated Dispositifs et systèmes de culture cellulaire à écoulement par gravité et procédés d'utilisation correspondants
WO2018067991A1 (fr) 2016-10-07 2018-04-12 The Brigham And Women's Hospital, Inc. Modulation de nouvelles cibles de points de contrôle immunitaires
WO2018081789A1 (fr) 2016-10-31 2018-05-03 Iovance Biotherapeutics, Inc. Cellules présentatrices d'antigènes artificielles génétiquement modifiées pour l'expansion de l'infiltration lymphocytaire intratumorale
WO2018081473A1 (fr) 2016-10-26 2018-05-03 Iovance Biotherapeutics, Inc. Re-stimulation de lymphocytes infiltrant les tumeurs cryoconservés
WO2018094167A1 (fr) 2016-11-17 2018-05-24 Iovance Biotherapeutics, Inc. Lymphocytes infiltrant les tumeurs restantes et leurs procédés de préparation et d'utilisation
WO2018111981A1 (fr) 2016-12-13 2018-06-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de préparation d'une population isolée ou purifiée de cellules thymiques émigrantes et procédés de traitement l'utilisant
WO2018129336A1 (fr) 2017-01-06 2018-07-12 Iovance Biotherapeutics, Inc. Expansion de lymphocytes infiltrant les tumeurs avec des agonistes des canaux potassiques et leurs utilisations thérapeutiques
WO2018129332A1 (fr) 2017-01-06 2018-07-12 Iovance Biotherapeutics, Inc. Expansion de lymphocytes infiltrant les tumeurs (til) avec des agonistes de la superfamille des récepteurs du facteur de nécrose tumorale (tnfrsf) et des combinaisons thérapeutiques de til et d'agonistes de tnfrsf
WO2018183485A1 (fr) 2017-03-31 2018-10-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de séquences de récepteur de lymphocytes t spécifiques à un néo-antigène
WO2018182817A1 (fr) 2017-03-29 2018-10-04 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2018191553A1 (fr) 2017-04-12 2018-10-18 Massachusetts Eye And Ear Infirmary Signature tumorale pour métastase, compositions de matière et leurs procédés d'utilisation
WO2018195019A1 (fr) 2017-04-18 2018-10-25 The Broad Institute Inc. Composition permettant de détecter une sécrétion et procédé d'utilisation
WO2018204761A1 (fr) * 2017-05-05 2018-11-08 H. Lee Moffitt Cancer Center And Research Institute, Inc. Procédé rapide de culture de lymphocytes infiltrant les tumeurs
WO2018209115A1 (fr) 2017-05-10 2018-11-15 Iovance Biotherapeutics, Inc. Expansion de lymphocytes infiltrant des tumeurs à partir de tumeurs liquides et leurs utilisations thérapeutiques
US10149898B2 (en) 2017-08-03 2018-12-11 Taiga Biotechnologies, Inc. Methods and compositions for the treatment of melanoma
WO2018226714A1 (fr) 2017-06-05 2018-12-13 Iovance Biotherapeutics, Inc. Procédés d'utilisation de lymphocytes infiltrant les tumeurs dans un mélanome doublement réfractaire
WO2019027465A1 (fr) 2017-08-03 2019-02-07 Taiga Biotechnologies, Inc. Méthodes et compositions pharmaceutiques destinées au traitement du mélanome
WO2019060336A1 (fr) 2017-09-20 2019-03-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Génération in vitro d'organoïde thymique à partir de cellules souches pluripotentes humaines
WO2019060349A1 (fr) 2017-09-20 2019-03-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t restreints au hla de classe ii contre kras muté
WO2019067242A1 (fr) 2017-09-29 2019-04-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de cellules t ayant une spécificité antigénique pour une mutation spécifique du cancer p53
WO2019067243A1 (fr) 2017-09-29 2019-04-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t reconnaissant p53 mutée
WO2019070435A1 (fr) 2017-10-05 2019-04-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Méthodes d'expansion sélective de cellules exprimant un tcr avec une région constante murine
WO2019075055A1 (fr) 2017-10-11 2019-04-18 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations de lymphocytes t au moyen d'inhibiteurs de mapk p38
WO2019077062A1 (fr) 2017-10-18 2019-04-25 Vivia Biotech, S.L. Cellules car-t activées par des bite
WO2019094983A1 (fr) 2017-11-13 2019-05-16 The Broad Institute, Inc. Méthodes et compositions de traitement du cancer par ciblage de la voie clec2d-klrb1
WO2019100023A1 (fr) 2017-11-17 2019-05-23 Iovance Biotherapeutics, Inc. Expansion de til à partir de produits d'aspiration d'aiguille fine et de petites biopsies
WO2019103857A1 (fr) 2017-11-22 2019-05-31 Iovance Biotherapeutics, Inc. Expansion de lymphocytes de sang périphérique (pbl) à partir de sang périphérique
US10316289B2 (en) 2012-09-06 2019-06-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of producing T memory stem cell populations
WO2019112932A1 (fr) 2017-12-04 2019-06-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Méthodes d'enrichissement de populations de cellules en lymphocytes t spécifiques du cancer à l'aide d'une stimulation in vitro de lymphocytes t mémoires
WO2019112941A1 (fr) 2017-12-04 2019-06-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t, limités à l'antigène hla de classe i, ayant une spécificité antigénique pour toute protéine ras mutée
WO2019118873A2 (fr) 2017-12-15 2019-06-20 Iovance Biotherapeutics, Inc. Systèmes et procédés pour déterminer l'administration bénéfique de lymphocytes infiltrant les tumeurs et leurs procédés d'utilisation, et administration bénéfique de lymphocytes infiltrant les tumeurs et ses procédés d'utilisation
US10344073B2 (en) * 2014-01-09 2019-07-09 Hadasit Medical Research Services And Development Ltd. Cell compositions and methods for cancer therapy
WO2019136456A1 (fr) 2018-01-08 2019-07-11 Iovance Biotherapeutics, Inc. Procédés de génération de produits de til enrichis pour des lymphocytes t spécifiques d'un antigène tumoral
WO2019136459A1 (fr) 2018-01-08 2019-07-11 Iovance Biotherapeutics, Inc. Procédés de génération de produits de til enrichis pour des lymphocytes t spécifiques d'un antigène tumoral
WO2019160829A1 (fr) 2018-02-13 2019-08-22 Iovance Biotherapeutics, Inc. Expansion de lymphocytes infiltrant les tumeurs (til) avec des antagonistes du récepteur a2a de l'adénosine et combinaisons thérapeutiques de til et d'antagonistes du récepteur a2a de l'adénosine
WO2019173441A1 (fr) 2018-03-06 2019-09-12 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de préparation de populations de cellules et de réactifs rétroviraux pour l'immunothérapie cellulaire adoptive
WO2019190579A1 (fr) 2018-03-29 2019-10-03 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2019209715A1 (fr) 2018-04-24 2019-10-31 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations de lymphocytes t faisant appel à de l'acide hydroxycitrique et/ou à un sel de celui-ci
WO2019210131A1 (fr) 2018-04-27 2019-10-31 Iovance Biotherapeutics, Inc. Procédé en circuit fermé pour l'amplification et l'edition de gènes de lymphocytes d'infiltration des tumeurs et leurs utilisations en immunothérapie
WO2019213195A1 (fr) 2018-05-01 2019-11-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t reconnaissant un egfr muté
WO2019217753A1 (fr) 2018-05-10 2019-11-14 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2019232542A2 (fr) 2018-06-01 2019-12-05 Massachusetts Institute Of Technology Procédés et compositions pour détecter et moduler des signatures géniques micro-environnementales à partir du lcr de patients présentant des métastases
EP3597663A1 (fr) 2014-12-08 2020-01-22 The U.S.A. as represented by the Secretary, Department of Health and Human Services Récepteurs d'antigènes chimères anti-cd70
US10562952B2 (en) 2015-09-10 2020-02-18 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-CD276 chimeric antigen receptors
WO2020061429A1 (fr) 2018-09-20 2020-03-26 Iovance Biotherapeutics, Inc. Expansion de til à partir d'échantillons de tumeur cryoconservés
WO2020068816A1 (fr) * 2018-09-24 2020-04-02 H. Lee Moffitt Cancer Center And Research Institute, Inc. Culture de lymphocytes infiltrant les tumeurs issus d'une digestion de tumeur
WO2020072700A1 (fr) 2018-10-02 2020-04-09 Dana-Farber Cancer Institute, Inc. Lignées d'allèles uniques d'alh
WO2020081730A2 (fr) 2018-10-16 2020-04-23 Massachusetts Institute Of Technology Méthodes et compositions pour moduler un microenvironnement
WO2020086827A1 (fr) 2018-10-24 2020-04-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t restreints au hla-a3 dirigés contre une ras mutée
WO2020096682A2 (fr) 2018-08-31 2020-05-14 Iovance Biotherapeutics, Inc. Traitement de patients souffrant de nsclc réfractaires à un anticorps anti-pd-1
WO2020096989A1 (fr) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Traitement de patients souffrant de nsclc réfractaires à un anticorps anti-pd-1
WO2020096986A2 (fr) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Sélection de lymphocytes t réactifs à une tumeur améliorés
WO2020096927A1 (fr) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Expansion de til utilisant des inhibiteurs de la voie akt
WO2020096988A2 (fr) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2020131547A1 (fr) 2018-12-19 2020-06-25 Iovance Biotherapeutics, Inc. Procédés pour la multiplication de lymphocytes infiltrant les tumeurs à l'aide de paires de récepteurs de cytokines modifiés et leurs utilisations
WO2020131586A2 (fr) 2018-12-17 2020-06-25 The Broad Institute, Inc. Méthodes d'identification de néo-antigènes
WO2020154275A1 (fr) 2019-01-22 2020-07-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe ii dirigés contre ras ayant une mutation g12r
WO2020172202A1 (fr) 2019-02-19 2020-08-27 Myst Therapeutics, Inc. Procédés de production de lymphocytes t autologues utilisés pour traiter les cancers, et compositions associées
US10760055B2 (en) 2005-10-18 2020-09-01 National Jewish Health Conditionally immortalized long-term stem cells and methods of making and using such cells
WO2020186101A1 (fr) 2019-03-12 2020-09-17 The Broad Institute, Inc. Procédés de détection, compositions et méthodes de modulation des cellules de sarcome synovial
WO2020191079A1 (fr) 2019-03-18 2020-09-24 The Broad Institute, Inc. Compositions et méthodes de modulation de régulateurs métaboliques de pathogénicité de lymphocytes t
US10786534B2 (en) 2013-03-11 2020-09-29 Taiga Biotechnologies, Inc. Production and use of red blood cells
WO2020205662A1 (fr) 2019-03-29 2020-10-08 Myst Therapeutics, Inc. Procédés ex vivo de production d'un agent thérapeutique de lymphocytes t et compositions et procédés associés
US10801070B2 (en) 2013-11-25 2020-10-13 The Broad Institute, Inc. Compositions and methods for diagnosing, evaluating and treating cancer
US10835585B2 (en) 2015-05-20 2020-11-17 The Broad Institute, Inc. Shared neoantigens
WO2020232029A1 (fr) 2019-05-13 2020-11-19 Iovance Biotherapeutics, Inc. Procédés et compositions pour sélectionner des lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2020236967A1 (fr) 2019-05-20 2020-11-26 The Broad Institute, Inc. Mutant de délétion de crispr-cas aléatoire
WO2020243371A1 (fr) 2019-05-28 2020-12-03 Massachusetts Institute Of Technology Procédés et compositions pour la modulation de réponses immunitaires
WO2020264269A1 (fr) 2019-06-27 2020-12-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs des lymphocytes t reconnaissant la mutation r175h ou y220c dans p53
WO2021030627A1 (fr) 2019-08-13 2021-02-18 The General Hospital Corporation Procédés de prédiction de résultats d'inhibition de point de contrôle et traitement associés
WO2021041922A1 (fr) 2019-08-30 2021-03-04 The Broad Institute, Inc. Systèmes de transposase mu associés à crispr
US10953048B2 (en) 2012-07-20 2021-03-23 Taiga Biotechnologies, Inc. Enhanced reconstitution and autoreconstitution of the hematopoietic compartment
WO2021055787A1 (fr) 2019-09-18 2021-03-25 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de populations de lymphocytes t
US10975442B2 (en) 2014-12-19 2021-04-13 Massachusetts Institute Of Technology Molecular biomarkers for cancer immunotherapy
WO2021081378A1 (fr) 2019-10-25 2021-04-29 Iovance Biotherapeutics, Inc. Édition génique de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2021092555A2 (fr) 2019-11-08 2021-05-14 Kiyatec, Inc. Méthodes de criblage pour déterminer le dosage efficace d'agents thérapeutiques anticancéreux
WO2021108727A1 (fr) 2019-11-27 2021-06-03 Myst Therapeutics, Inc. Procédé de production d'une composition de lymphocytes t réactifs à une tumeur faisant appel à des agents modulateurs
WO2021118990A1 (fr) 2019-12-11 2021-06-17 Iovance Biotherapeutics, Inc. Procédés pour la production de lymphocytes infiltrant les tumeurs (til) et leurs procédés d'utilisation
CN113005085A (zh) * 2021-03-18 2021-06-22 南方医科大学南方医院 一种新型的原发性肝癌肿瘤浸润淋巴细胞的培养及体外扩增方法
WO2021142081A1 (fr) 2020-01-07 2021-07-15 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations de lymphocytes t au moyen de cellules souches pluripotentes induites
WO2021163434A1 (fr) 2020-02-12 2021-08-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe i dirigés contre ras ayant une mutation g12d
WO2021163477A1 (fr) 2020-02-14 2021-08-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe ii dirigés contre ras ayant une mutation g12v
WO2021174208A1 (fr) 2020-02-27 2021-09-02 Myst Therapeutics, Llc Procédés d'enrichissement et d'expansion ex vivo de lymphocytes t réactifs à une tumeur et compositions associées
WO2021173902A1 (fr) 2020-02-26 2021-09-02 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe ii dirigés contre ras ayant une mutation g12v
US11116796B2 (en) 2016-12-02 2021-09-14 Taiga Biotechnologies, Inc. Nanoparticle formulations
WO2021188954A1 (fr) 2020-03-20 2021-09-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de lymphocytes t et de récepteurs de lymphocytes t à partir d'une tumeur par analyse de cellules uniques pour immunothérapie
WO2021188941A1 (fr) 2020-03-20 2021-09-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de lymphocytes t et de récepteurs de lymphocytes t à partir de sang périphérique par analyse à une seule cellule pour l'immunothérapie
US11141434B2 (en) 2016-07-07 2021-10-12 Iovance Biotherapeutics, Inc. Programmed death 1 ligand 1 (PD-L1) binding proteins and methods of use thereof
WO2021211455A1 (fr) 2020-04-13 2021-10-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe i contre lmp2
WO2021216920A1 (fr) 2020-04-22 2021-10-28 Iovance Biotherapeutics, Inc. Systèmes et procédés pour coordonner la fabrication de cellules pour l'immunothérapie spécifique au patient
WO2021226085A1 (fr) 2020-05-04 2021-11-11 Iovance Biotherapeutics, Inc. Sélection de lymphocytes t réactifs à une tumeur améliorés
WO2021226061A1 (fr) 2020-05-04 2021-11-11 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2021262829A2 (fr) 2020-06-24 2021-12-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t limités au hla de classe i contre le cd20
WO2022015922A1 (fr) 2020-07-16 2022-01-20 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t drb à restriction hla de classe ii dirigés contre ras, comprenant une mutation g12v
WO2022015694A1 (fr) 2020-07-13 2022-01-20 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe ii dirigés contre ras ayant une mutation g12d
US11254913B1 (en) 2017-03-29 2022-02-22 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
WO2022051449A2 (fr) 2020-09-04 2022-03-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs des lymphocytes t reconnaissant les mutations r175h ou y220c dans p53
WO2022055946A1 (fr) 2020-09-08 2022-03-17 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Phénotypes de lymphocytes t associés à une réponse à une thérapie cellulaire adoptive
WO2022072760A1 (fr) 2020-10-02 2022-04-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe ii dirigés contre ras ayant une mutation g13d
WO2022076606A1 (fr) 2020-10-06 2022-04-14 Iovance Biotherapeutics, Inc. Traitement de patients souffrant de cpnpc avec des thérapies de lymphocytes infiltrant les tumeurs
WO2022076952A1 (fr) 2020-10-06 2022-04-14 Iovance Biotherapeutics, Inc. Traitement de patients souffrant de cpnpc avec des thérapies lymphocytaires infiltrant les tumeurs
WO2022104035A2 (fr) 2020-11-13 2022-05-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Réactivité antigénique améliorée de cellules immunitaires exprimant une chaîne zêta cd3 de non-signalisation mutante
WO2022105816A1 (fr) * 2020-11-19 2022-05-27 苏州沙砾生物科技有限公司 Procédé de culture de lymphocytes infiltrant les tumeurs et son utilisation
WO2022125941A1 (fr) 2020-12-11 2022-06-16 Iovance Biotherapeutics, Inc. Traitement de patients atteints de cancer par des thérapies de lymphocytes infiltrant les tumeurs en combinaison avec des inhibiteurs de braf et/ou des inhibiteurs de mek
WO2022133149A1 (fr) 2020-12-17 2022-06-23 Iovance Biotherapeutics, Inc. Traitement de cancers à l'aide de lymphocytes infiltrant les tumeurs
WO2022133140A1 (fr) 2020-12-17 2022-06-23 Iovance Biotherapeutics, Inc. Traitement avec des thérapies de lymphocytes infiltrant les tumeurs en combinaison avec des inhibiteurs de ctla-4 et de pd-1
US11369678B2 (en) 2008-08-28 2022-06-28 Taiga Biotechnologies, Inc. Compositions and methods for modulating immune cells
WO2022147196A2 (fr) 2020-12-31 2022-07-07 Iovance Biotherapeutics, Inc. Dispositifs et procédés de production automatisée de lymphocytes infiltrant les tumeurs
CN114763530A (zh) * 2021-01-15 2022-07-19 上海细胞治疗集团有限公司 一种诱导和制备til细胞的方法
US11401506B2 (en) 2014-04-10 2022-08-02 H. Lee Moffitt Cancer Center And Research Institute, Inc. Enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy
WO2022170219A1 (fr) 2021-02-05 2022-08-11 Iovance Biotherapeutics, Inc. Traitement adjuvant du cancer
WO2022177961A1 (fr) 2021-02-16 2022-08-25 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe i contre cd22
WO2022187741A2 (fr) 2021-03-05 2022-09-09 Iovance Biotherapeutics, Inc. Stockage de tumeur et compositions de culture cellulaire
WO2022198141A1 (fr) 2021-03-19 2022-09-22 Iovance Biotherapeutics, Inc. Procédés pour la multiplication des lymphocytes infiltrant les tumeurs (til) liés à la sélection de cd39/cd69 et inactivation de gènes dans les til
US11452768B2 (en) 2013-12-20 2022-09-27 The Broad Institute, Inc. Combination therapy with neoantigen vaccine
WO2022204564A2 (fr) 2021-03-25 2022-09-29 Iovance Biotherapeutics, Inc. Procédés et compositions pour dosages de puissance de coculture de lymphocytes t et utilisation avec des produits de thérapie cellulaire
WO2022204155A1 (fr) 2021-03-23 2022-09-29 Iovance Biotherapeutics, Inc. Édition génique cish de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2022225836A1 (fr) 2021-04-21 2022-10-27 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe i dirigés contre ras ayant une mutation q61k
WO2022225981A2 (fr) 2021-04-19 2022-10-27 Iovance Biotherapeutics, Inc. Récepteurs costimulateurs chimériques, récepteurs de chimiokines et leur utilisation dans des immunothérapies cellulaires
WO2022236050A1 (fr) 2021-05-07 2022-11-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t reconnaissant les mutations c135y, r175h, ou m237i dans p53
WO2022245754A1 (fr) 2021-05-17 2022-11-24 Iovance Biotherapeutics, Inc. Lymphocytes infiltrant les tumeurs modifiés par un gène pd-1 et leurs utilisations en immunothérapie
US11530386B2 (en) 2015-12-15 2022-12-20 Instil Bio (Uk) Limited Cells expressing recombinant growth factor receptors
US11549149B2 (en) 2017-01-24 2023-01-10 The Broad Institute, Inc. Compositions and methods for detecting a mutant variant of a polynucleotide
WO2023009716A1 (fr) 2021-07-28 2023-02-02 Iovance Biotherapeutics, Inc. Traitement de patients atteints d'un cancer avec des thérapies de lymphocytes infiltrant les tumeurs en combinaison avec des inhibiteurs de kras
WO2023039488A1 (fr) 2021-09-09 2023-03-16 Iovance Biotherapeutics, Inc. Procédés de production de produits til par inactivation de pd-1 avec talen
WO2023049862A1 (fr) 2021-09-24 2023-03-30 Iovance Biotherapeutics, Inc. Processus d'expansion et agents pour lymphocytes infiltrant la tumeur
US11618877B2 (en) 2017-01-13 2023-04-04 Instil Bio (Uk) Limited Aseptic tissue processing method, kit and device
WO2023077015A2 (fr) 2021-10-27 2023-05-04 Iovance Biotherapeutics, Inc. Systèmes et méthodes pour coordonner la fabrication de cellules pour l'immunothérapie spécifique d'un patient
WO2023086803A1 (fr) 2021-11-10 2023-05-19 Iovance Biotherapeutics, Inc. Procédés de traitement de multiplication utilisant des lymphocytes infiltrant les tumeurs cd8
US11667695B2 (en) 2008-05-16 2023-06-06 Taiga Biotechnologies, Inc. Antibodies and processes for preparing the same
WO2023102418A1 (fr) 2021-12-01 2023-06-08 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla-a3 contre ras avec mutation g12v
WO2023137472A2 (fr) 2022-01-14 2023-07-20 Tune Therapeutics, Inc. Compositions, systèmes et procédés de programmation de phénotypes de lymphocytes t par répression génique ciblée
WO2023137471A1 (fr) 2022-01-14 2023-07-20 Tune Therapeutics, Inc. Compositions, systèmes et procédés de programmation de phénotypes de lymphocytes t par activation génique ciblée
US11713446B2 (en) 2018-01-08 2023-08-01 Iovance Biotherapeutics, Inc. Processes for generating TIL products enriched for tumor antigen-specific T-cells
WO2023147486A1 (fr) 2022-01-28 2023-08-03 Iovance Biotherapeutics, Inc. Lymphocytes infiltrant les tumeurs modifiés pour exprimer des charges utiles
US11725237B2 (en) 2013-12-05 2023-08-15 The Broad Institute Inc. Polymorphic gene typing and somatic change detection using sequencing data
US11732257B2 (en) 2017-10-23 2023-08-22 Massachusetts Institute Of Technology Single cell sequencing libraries of genomic transcript regions of interest in proximity to barcodes, and genotyping of said libraries
US11739156B2 (en) 2019-01-06 2023-08-29 The Broad Institute, Inc. Massachusetts Institute of Technology Methods and compositions for overcoming immunosuppression
US11767510B2 (en) 2019-12-20 2023-09-26 Instil Bio (Uk) Limited Devices and methods for isolating tumor infiltrating lymphocytes and uses thereof
WO2023196877A1 (fr) 2022-04-06 2023-10-12 Iovance Biotherapeutics, Inc. Traitement de patients souffrant de cpnpc avec des thérapies lymphocytaires infiltrant les tumeurs
WO2023201369A1 (fr) 2022-04-15 2023-10-19 Iovance Biotherapeutics, Inc. Processus d'expansion de til utilisant des combinaisons spécifiques de cytokine et/ou traitement akti
US11793787B2 (en) 2019-10-07 2023-10-24 The Broad Institute, Inc. Methods and compositions for enhancing anti-tumor immunity by targeting steroidogenesis
WO2023220608A1 (fr) 2022-05-10 2023-11-16 Iovance Biotherapeutics, Inc. Traitement de patients atteints d'un cancer avec des thérapies lymphocytaires infiltrant les tumeurs en combinaison avec un agoniste d'il-15r
US11834487B2 (en) 2018-02-12 2023-12-05 Hadasit Medical Research Services & Development Ltd. Modulation of SLAMF6 splice variants for cancer therapy
US11865168B2 (en) 2019-12-30 2024-01-09 Massachusetts Institute Of Technology Compositions and methods for treating bacterial infections
WO2024011114A1 (fr) 2022-07-06 2024-01-11 Iovance Biotherapeutics, Inc. Dispositifs et procédés de production automatisée de lymphocytes infiltrant les tumeurs
WO2024030758A1 (fr) 2022-08-01 2024-02-08 Iovance Biotherapeutics, Inc. Récepteurs de costimulation chimériques, récepteurs de chimiokines et leur utilisation dans des immunothérapies cellulaires
US11897953B2 (en) 2017-06-14 2024-02-13 The Broad Institute, Inc. Compositions and methods targeting complement component 3 for inhibiting tumor growth
US11913075B2 (en) 2017-04-01 2024-02-27 The Broad Institute, Inc. Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer
WO2024055017A1 (fr) 2022-09-09 2024-03-14 Iovance Biotherapeutics, Inc. Procédés de génération de produits til à l'aide d'une double inactivation de talen pd-1/tigit
WO2024055018A1 (fr) 2022-09-09 2024-03-14 Iovance Biotherapeutics, Inc. Procédés de génération de produits til à l'aide d'une double inactivation talen de pd-1/tigit
WO2024064642A2 (fr) 2022-09-19 2024-03-28 Tune Therapeutics, Inc. Compositions, systèmes et méthodes de modulation de fonction de lymphocyte t
US11957695B2 (en) 2018-04-26 2024-04-16 The Broad Institute, Inc. Methods and compositions targeting glucocorticoid signaling for modulating immune responses
US11963966B2 (en) 2017-03-31 2024-04-23 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating ovarian tumors
US11981922B2 (en) 2020-10-05 2024-05-14 Dana-Farber Cancer Institute, Inc. Methods and compositions for the modulation of cell interactions and signaling in the tumor microenvironment

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013167136A1 (fr) * 2012-05-08 2013-11-14 Herlev Hospital Amélioration de la thérapie cellulaire adoptive avec l'interféron gamma
EP3838288A1 (fr) 2014-06-11 2021-06-23 polybiocept GmbH Expansion de lymphocytes avec une composition de cytokine pour immunothérapie cellulaire active
US11261428B2 (en) 2018-03-15 2022-03-01 KSQ Therapeutics, Inc. Gene-regulating compositions and methods for improved immunotherapy
US11332713B2 (en) 2016-11-16 2022-05-17 KSQ Therapeutics, Inc. Gene-regulating compositions and methods for improved immunotherapy
EP3765094A4 (fr) 2018-03-15 2021-12-22 KSQ Therapeutics, Inc. Compositions de régulation génique et procédés pour améliorer l'immunothérapie
JP2024512978A (ja) * 2021-03-30 2024-03-21 ネオジェント コーポレーション 免疫細胞組成物を生成するための方法
WO2022271847A1 (fr) * 2021-06-24 2022-12-29 Instil Bio, Inc. Traitement de lymphocytes d'infiltration tumorale
WO2023130040A2 (fr) 2021-12-31 2023-07-06 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Thérapie par lymphocytes t avec vaccination en tant que polythérapie immunitaire contre le cancer

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050233451A1 (en) * 2002-10-15 2005-10-20 Government Of The United States Of America, Represented By The Sec. Dept. Of Health And Humans Methods of preparing lymphocytes that express interleukin-2 and their use in the treatment of cancer
US20130102075A1 (en) * 2009-12-08 2013-04-25 Juan F. Vera Methods of cell culture for adoptive cell therapy

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4435508A (en) 1981-11-20 1984-03-06 Gabridge Michael G Tissue culture vessel
EP0471947A1 (fr) 1990-06-29 1992-02-26 Sekisui Chemical Co., Ltd. Sac de culture
DE69931800T2 (de) 1998-10-28 2007-07-12 Cellon S.A. Strukturierter und poröser silikonkautschuk
US6455310B1 (en) 1999-03-23 2002-09-24 Biocrystal Ltd. Cell culture apparatus and method for culturing cells
US6410309B1 (en) 1999-03-23 2002-06-25 Biocrystal Ltd Cell culture apparatus and methods of use
US9255243B2 (en) 2003-10-08 2016-02-09 Wilson Wolf Manufacturing Corporation Cell culture methods and devices utilizing gas permeable materials
US7820174B2 (en) 2006-02-24 2010-10-26 The United States Of America As Represented By The Department Of Health And Human Services T cell receptors and related materials and methods of use
WO2010126766A1 (fr) 2009-04-30 2010-11-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Interleukine-12 inductible
SG181559A1 (en) * 2009-12-08 2012-07-30 Wolf Wilson Mfg Corp Improved methods of cell culture for adoptive cell therapy

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050233451A1 (en) * 2002-10-15 2005-10-20 Government Of The United States Of America, Represented By The Sec. Dept. Of Health And Humans Methods of preparing lymphocytes that express interleukin-2 and their use in the treatment of cancer
US20130102075A1 (en) * 2009-12-08 2013-04-25 Juan F. Vera Methods of cell culture for adoptive cell therapy

Cited By (350)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10760055B2 (en) 2005-10-18 2020-09-01 National Jewish Health Conditionally immortalized long-term stem cells and methods of making and using such cells
US11667695B2 (en) 2008-05-16 2023-06-06 Taiga Biotechnologies, Inc. Antibodies and processes for preparing the same
US11369678B2 (en) 2008-08-28 2022-06-28 Taiga Biotechnologies, Inc. Compositions and methods for modulating immune cells
US10953048B2 (en) 2012-07-20 2021-03-23 Taiga Biotechnologies, Inc. Enhanced reconstitution and autoreconstitution of the hematopoietic compartment
US11111478B2 (en) 2012-09-06 2021-09-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of producing T memory stem cell populations
US10316289B2 (en) 2012-09-06 2019-06-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of producing T memory stem cell populations
CN111643524A (zh) * 2013-03-01 2020-09-11 美国卫生和人力服务部 从外周血中产生肿瘤反应性t细胞富集群的方法
US10716809B2 (en) 2013-03-01 2020-07-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of producing enriched populations of tumor reactive T cells from peripheral blood
US9844569B2 (en) 2013-03-01 2017-12-19 The United State Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of producing enriched populations of tumor reactive T cells from peripheral blood
US11679128B2 (en) 2013-03-01 2023-06-20 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of producing enriched populations of tumor reactive T cells from peripheral blood
EP3821898A1 (fr) 2013-03-01 2021-05-19 The United States of America, as represented by The Secretary, Department of Health and Human Services Procédés de production de populations enrichies de lymphocytes t réactifs à une tumeur à partir d'une tumeur
WO2014133567A1 (fr) 2013-03-01 2014-09-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations enrichies de lymphocytes t réactifs à une tumeur à partir d'une tumeur
WO2014133568A1 (fr) 2013-03-01 2014-09-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations enrichies de lymphocytes t réactifs à une tumeur à partir de sang périphérique
EP3628322A1 (fr) 2013-03-01 2020-04-01 The United States of America, as represented by the Secretary, Department of Health and Human Services Cellules t cd8 + qui expriment également pd-1 et / ou tim-3 pour le traitement du cancer
US10786534B2 (en) 2013-03-11 2020-09-29 Taiga Biotechnologies, Inc. Production and use of red blood cells
US10913785B2 (en) 2013-07-15 2021-02-09 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-human papillomavirus 16 E6 T cell receptors
WO2015009606A1 (fr) 2013-07-15 2015-01-22 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t anti-papillomavirus humain 16 e6
US11331385B2 (en) 2013-07-15 2022-05-17 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of preparing anti-human papillomavirus antigen T cells
US11338032B2 (en) 2013-07-15 2022-05-24 The United States of Americans represented by the Secretary, Department of Health and Human Services Methods of preparing anti-human papillomavirus antigen T cells
EP3626817A1 (fr) 2013-07-15 2020-03-25 The United States of America, as represented by the Secretary, Department of Health and Human Services Procédés de préparation de lymphocytes t antigènes du papillomavirus humain
US11376318B2 (en) 2013-07-15 2022-07-05 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of preparing anti-human papillomavirus antigen t cells
US11697676B2 (en) 2013-07-15 2023-07-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-human papillomavirus 16 E6 T cell receptors
US10329339B2 (en) 2013-07-15 2019-06-25 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-human papillomavirus 16 E6 T cell receptors
CN111733131A (zh) * 2013-07-15 2020-10-02 美国卫生和人力服务部 制备抗人乳头瘤病毒抗原的t细胞的方法
US11077182B2 (en) 2013-07-15 2021-08-03 The United States of Americans represented by the Secretary, Department of Health and Human Services Methods of preparing anti-human papillomavirus antigen T cells
US9822162B2 (en) 2013-07-15 2017-11-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-human papillomavirus 16 E6 T cell receptors
US11918640B2 (en) 2013-07-15 2024-03-05 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of preparing anti-human papillomavirus antigen T cells
WO2015009604A1 (fr) 2013-07-15 2015-01-22 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de préparation de cellules t antigéniques anti-papillomavirus humain
EP3572423A1 (fr) 2013-07-15 2019-11-27 The U.S.A. as represented by the Secretary, Department of Health and Human Services Récepteurs de lymphocytes t anti-papillomavirus humain 16 e6
EP4137564A1 (fr) 2013-07-15 2023-02-22 The United States of America, as represented by the Secretary, Department of Health and Human Services Procédés de préparation de lymphocytes t anti-antigène du papillomavirus humain
US10801070B2 (en) 2013-11-25 2020-10-13 The Broad Institute, Inc. Compositions and methods for diagnosing, evaluating and treating cancer
US11834718B2 (en) 2013-11-25 2023-12-05 The Broad Institute, Inc. Compositions and methods for diagnosing, evaluating and treating cancer by means of the DNA methylation status
US11725237B2 (en) 2013-12-05 2023-08-15 The Broad Institute Inc. Polymorphic gene typing and somatic change detection using sequencing data
US11452768B2 (en) 2013-12-20 2022-09-27 The Broad Institute, Inc. Combination therapy with neoantigen vaccine
US11530251B2 (en) 2014-01-09 2022-12-20 Hadasit Medical Research Services And Development Ltd. Methods for cancer therapy using isolated NTB-A ectodomain polypeptides
US10344073B2 (en) * 2014-01-09 2019-07-09 Hadasit Medical Research Services And Development Ltd. Cell compositions and methods for cancer therapy
US11401506B2 (en) 2014-04-10 2022-08-02 H. Lee Moffitt Cancer Center And Research Institute, Inc. Enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy
EP3689900A1 (fr) 2014-05-29 2020-08-05 The United States of America, as represented by The Secretary, Department of Health and Human Services Vecteurs d'expression pour récepteurs de lymphocytes t anti-papillomavirus humain 16 e7
US10870687B2 (en) 2014-05-29 2020-12-22 The United States Of America, As Represented By The Secretary, Department Of Health And Human Service Anti-human papillomavirus 16 E7 T cell receptors
US10174098B2 (en) 2014-05-29 2019-01-08 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-human papillomavirus 16 E7 T cell receptors
US11434272B2 (en) 2014-05-29 2022-09-06 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-human papillomavirus 16 E7 T cell receptors
WO2015184228A1 (fr) 2014-05-29 2015-12-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t anti-papillomavirus humain 16 e7
EP3848456A1 (fr) 2014-10-02 2021-07-14 The United States of America, as represented by The Secretary, Department of Health and Human Services Méthodes d'isolation de cellules t présentant une spécificité antigénique pour une mutation spécifique d'un cancer
WO2016053338A1 (fr) 2014-10-02 2016-04-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de récepteurs des lymphocytes t présentant une spécificité antigénique pour une mutation spécifique du cancer
WO2016053339A1 (fr) 2014-10-02 2016-04-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Méthodes d'isolation de cellules t présentant une spécificité antigénique pour une mutation spécifique d'un cancer
EP4074333A1 (fr) 2014-10-02 2022-10-19 The United States of America, as represented by the Secretary, Department of Health and Human Services Procédés d'isolement de récepteurs des lymphocytes t présentant une spécificité antigénique pour une mutation spécifique du cancer
US10973894B2 (en) 2014-10-02 2021-04-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Methods of isolating T cells having antigenic specificity for a cancer-specific mutation
WO2016077525A2 (fr) 2014-11-14 2016-05-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t anti-thyroblobuline humaine
EP3808770A1 (fr) 2014-11-14 2021-04-21 The U.S.A. as represented by the Secretary, Department of Health and Human Services Récepteurs cellulaires t humains anti-thyroglobuline
US10450372B2 (en) 2014-11-14 2019-10-22 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-thyroglobulin T cell receptors
US11440956B2 (en) 2014-11-14 2022-09-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-thyroglobulin T cell receptors
EP3666288A1 (fr) 2014-11-26 2020-06-17 The United States of America, as represented by The Secretary, Department of Health and Human Services Récepteurs de lymphocytes t kras anti-mutation
WO2016085904A1 (fr) 2014-11-26 2016-06-02 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t kras anti-mutation
US11207394B2 (en) 2014-11-26 2021-12-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-mutated KRAS T cell receptors
EP4286407A2 (fr) 2014-11-26 2023-12-06 The United States of America, as represented by The Secretary, Department of Health and Human Services Récepteurs de lymphocytes t kras anti-mutation
EP3597663A1 (fr) 2014-12-08 2020-01-22 The U.S.A. as represented by the Secretary, Department of Health and Human Services Récepteurs d'antigènes chimères anti-cd70
US10689456B2 (en) 2014-12-08 2020-06-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-CD70 chimeric antigen receptors
EP4043487A1 (fr) 2014-12-08 2022-08-17 The United States of America, as represented by The Secretary, Department of Health and Human Services Récepteurs d'antigènes chimères anti-cd70
US10975442B2 (en) 2014-12-19 2021-04-13 Massachusetts Institute Of Technology Molecular biomarkers for cancer immunotherapy
WO2016100977A1 (fr) 2014-12-19 2016-06-23 The Broad Institute Inc. Procédés pour le profilage du répertoire de récepteurs de cellules t
EP3757211A1 (fr) 2014-12-19 2020-12-30 The Broad Institute, Inc. Procédés pour le profilage de répertoire de récepteurs de lymphocytes t
US11939637B2 (en) 2014-12-19 2024-03-26 Massachusetts Institute Of Technology Molecular biomarkers for cancer immunotherapy
US10993997B2 (en) 2014-12-19 2021-05-04 The Broad Institute, Inc. Methods for profiling the t cell repertoire
WO2016138182A1 (fr) * 2015-02-24 2016-09-01 Nodality, Inc. Méthodes et compositions d'immunomodulation
WO2016179006A1 (fr) 2015-05-01 2016-11-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de cellules t et de récepteurs des cellules t ayant une spécificité antigénique pour une mutation spécifique au cancer du sang périphérique
US10544392B2 (en) 2015-05-01 2020-01-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of isolating T cells and T cell receptors having antigenic specificity for a cancer-specific mutation from peripheral blood
US11629334B2 (en) 2015-05-01 2023-04-18 The United States of Americans represented by the Secretary, Department of Health and Human Services Methods of isolating T cells and T cell receptors having antigenic specificity for a cancer-specific mutation from peripheral blood
US10835585B2 (en) 2015-05-20 2020-11-17 The Broad Institute, Inc. Shared neoantigens
WO2017035251A1 (fr) 2015-08-25 2017-03-02 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Lymphocytes t modifiés pour surexprimer la c-myb
US11098283B2 (en) 2015-08-25 2021-08-24 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services T cells modified to overexpress c-Myb
US10562952B2 (en) 2015-09-10 2020-02-18 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-CD276 chimeric antigen receptors
US10556940B2 (en) 2015-09-15 2020-02-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services T cell receptors recognizing HLA-Cw8 restricted mutated KRAS
US11667692B2 (en) 2015-09-15 2023-06-06 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services T cell receptors recognizing HLA-CW8 restricted mutated KRAS
EP3901169A1 (fr) 2015-09-15 2021-10-27 The United States of America, as represented by the Secretary, Department of Health and Human Services Récepteurs de lymphocytes t reconnaissant les gènes kras mutés limités en hla-cw8
WO2017048593A1 (fr) 2015-09-15 2017-03-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t reconnaissant les gènes kras mutés limités en hla-cw8
WO2017069958A2 (fr) 2015-10-09 2017-04-27 The Brigham And Women's Hospital, Inc. Modulation de nouvelles cibles de points de contrôle immunitaires
US10815301B2 (en) 2015-10-15 2020-10-27 The United States Of America, As Represented By The Secretary, Department Of Health And Human Service Anti-CD30 chimeric antigen receptors
WO2017066122A1 (fr) 2015-10-15 2017-04-20 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs antigéniques chimériques anti-cd30
WO2017070042A1 (fr) 2015-10-20 2017-04-27 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations de lymphocytes t à l'aide d'inhibiteurs d'akt
WO2017075465A1 (fr) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions et procédés d'évaluation et de modulation des réponses immunitaires par détection et ciblage de gata3
WO2017075451A1 (fr) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions et procédés d'évaluation et de modulation des réponses immunitaires par détection et ciblage de pou2af1
WO2017075478A2 (fr) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions et méthodes d'évaluation et de modulation des réponses immunitaires à l'aide de signatures génétiques de cellules immunitaires
US11180730B2 (en) 2015-10-28 2021-11-23 The Broad Institute, Inc. Compositions and methods for evaluating and modulating immune responses by detecting and targeting GATA3
US11186825B2 (en) 2015-10-28 2021-11-30 The Broad Institute, Inc. Compositions and methods for evaluating and modulating immune responses by detecting and targeting POU2AF1
WO2017079113A1 (fr) 2015-11-02 2017-05-11 The United States Of America, As Represented By The Secretary, Department Of Healh And Human Services Procédés de production de populations de lymphocytes t à l'aide d'inhibiteurs de protéines contenant un domaine prolyl hydroxylase
US11001622B2 (en) 2015-11-19 2021-05-11 The Brigham And Women's Hospital, Inc. Method of treating autoimmune disease with lymphocyte antigen CD5-like (CD5L) protein
WO2017087708A1 (fr) 2015-11-19 2017-05-26 The Brigham And Women's Hospital, Inc. Hétérodimères dans l'immunité de l'interleukine 12b (p40) de type antigène lymphocytaire cd5 (cd5l)
US11884717B2 (en) 2015-11-19 2024-01-30 The Brigham And Women's Hospital, Inc. Method of treating autoimmune disease with lymphocyte antigen CD5-like (CD5L) protein
US11530386B2 (en) 2015-12-15 2022-12-20 Instil Bio (Uk) Limited Cells expressing recombinant growth factor receptors
WO2017139199A1 (fr) 2016-02-10 2017-08-17 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Arginase inductible
WO2017178572A1 (fr) 2016-04-13 2017-10-19 Vivia Biotech, S.L Cellules t destructrices de cellules tumorales et leurs utilisations
WO2017189254A1 (fr) 2016-04-26 2017-11-02 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t anti-kk-lc-1
US11352410B2 (en) 2016-04-26 2022-06-07 The United States of American, as represented by the Secretary, Department of Health and Human Service Anti-KK-LC-1 T cell receptors
US11141434B2 (en) 2016-07-07 2021-10-12 Iovance Biotherapeutics, Inc. Programmed death 1 ligand 1 (PD-L1) binding proteins and methods of use thereof
WO2018026691A1 (fr) 2016-08-02 2018-02-08 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs des lymphocytes t anti-kras-g12d
US11897933B2 (en) 2016-08-02 2024-02-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-KRAS-G12D T cell receptors
US11840561B2 (en) 2016-08-02 2023-12-12 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-KRAS-G12D T cell receptors
US11208456B2 (en) 2016-08-02 2021-12-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-KRAS-G12D T cell receptors
US10611816B2 (en) 2016-08-02 2020-04-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-KRAS-G12D T cell receptors
EP4159751A1 (fr) 2016-08-02 2023-04-05 The United States of America, as represented by the Secretary, Department of Health and Human Services Récepteurs des lymphocytes t anti-kras-g12d
WO2018049025A2 (fr) 2016-09-07 2018-03-15 The Broad Institute Inc. Compositions et procédés pour évaluer et moduler des réponses immunitaires
WO2018057769A1 (fr) 2016-09-22 2018-03-29 Corning Incorporated Dispositifs et systèmes de culture cellulaire à écoulement par gravité et procédés d'utilisation correspondants
WO2018067991A1 (fr) 2016-10-07 2018-04-12 The Brigham And Women's Hospital, Inc. Modulation de nouvelles cibles de points de contrôle immunitaires
US11351199B2 (en) 2016-10-26 2022-06-07 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
EP4180520A1 (fr) 2016-10-26 2023-05-17 Iovance Biotherapeutics, Inc. Re-stimulation de lymphocytes infiltrant les tumeurs cryoconservés
US11369637B2 (en) 2016-10-26 2022-06-28 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11058728B1 (en) 2016-10-26 2021-07-13 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11026974B2 (en) 2016-10-26 2021-06-08 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11344581B2 (en) 2016-10-26 2022-05-31 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11344580B2 (en) 2016-10-26 2022-05-31 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11975028B2 (en) 2016-10-26 2024-05-07 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11364266B2 (en) 2016-10-26 2022-06-21 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11351197B2 (en) 2016-10-26 2022-06-07 Iovante Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11304980B2 (en) 2016-10-26 2022-04-19 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11123371B2 (en) 2016-10-26 2021-09-21 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11266694B2 (en) 2016-10-26 2022-03-08 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11311578B2 (en) 2016-10-26 2022-04-26 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11865140B2 (en) 2016-10-26 2024-01-09 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11141438B2 (en) 2016-10-26 2021-10-12 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11179419B2 (en) 2016-10-26 2021-11-23 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11351198B2 (en) 2016-10-26 2022-06-07 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
WO2018081473A1 (fr) 2016-10-26 2018-05-03 Iovance Biotherapeutics, Inc. Re-stimulation de lymphocytes infiltrant les tumeurs cryoconservés
US11969444B2 (en) 2016-10-26 2024-04-30 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US10517894B2 (en) 2016-10-26 2019-12-31 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
US11857573B2 (en) 2016-10-26 2024-01-02 Iovance Biotherapeutics, Inc. Restimulation of cryopreserved tumor infiltrating lymphocytes
WO2018081789A1 (fr) 2016-10-31 2018-05-03 Iovance Biotherapeutics, Inc. Cellules présentatrices d'antigènes artificielles génétiquement modifiées pour l'expansion de l'infiltration lymphocytaire intratumorale
US11667890B2 (en) 2016-10-31 2023-06-06 Iovance Biotherapeutics, Inc. Engineered artificial antigen presenting cells for tumor infiltrating lymphocyte expansion
US10415015B2 (en) 2016-10-31 2019-09-17 Iovance Biotherapeutics, Inc. Engineered artificial antigen presenting cells for tumor infiltrating lymphocyte expansion
JP7125392B2 (ja) 2016-11-17 2022-08-24 アイオバンス バイオセラピューティクス，インコーポレイテッド レムナント腫瘍浸潤リンパ球並びにそれを調製及び使用する方法
US11401507B2 (en) 2016-11-17 2022-08-02 Iovance Biotherapeutics, Inc. Remnant tumor infiltrating lymphocytes and methods of preparing and using the same
CN110199016A (zh) * 2016-11-17 2019-09-03 艾欧凡斯生物治疗公司 残余肿瘤浸润淋巴细胞及其制备和使用方法
TWI826360B (zh) * 2016-11-17 2023-12-21 美商艾歐凡斯生物治療公司 殘餘腫瘤浸潤性淋巴細胞及製備和使用彼之方法
KR102618948B1 (ko) 2016-11-17 2023-12-27 이오반스 바이오테라퓨틱스, 인크. 잔유 종양 침윤 림프구 및 그의 제조 및 사용 방법
KR20190084101A (ko) * 2016-11-17 2019-07-15 이오반스 바이오테라퓨틱스, 인크. 잔유 종양 침윤 림프구 및 그의 제조 및 사용 방법
US11293009B2 (en) * 2016-11-17 2022-04-05 Iovance Biotherapeutics, Inc. Remnant tumor infiltrating lymphocytes and methods of preparing and using the same
WO2018094167A1 (fr) 2016-11-17 2018-05-24 Iovance Biotherapeutics, Inc. Lymphocytes infiltrant les tumeurs restantes et leurs procédés de préparation et d'utilisation
US11220670B2 (en) 2016-11-17 2022-01-11 Iovance Biotherapeutics, Inc. Remnant tumor infiltrating lymphocytes and methods of preparing and using the same
JP2019534030A (ja) * 2016-11-17 2019-11-28 アイオバンス バイオセラピューティクス，インコーポレイテッド レムナント腫瘍浸潤リンパ球並びにそれを調製及び使用する方法
US11116796B2 (en) 2016-12-02 2021-09-14 Taiga Biotechnologies, Inc. Nanoparticle formulations
WO2018111981A1 (fr) 2016-12-13 2018-06-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de préparation d'une population isolée ou purifiée de cellules thymiques émigrantes et procédés de traitement l'utilisant
WO2018129336A1 (fr) 2017-01-06 2018-07-12 Iovance Biotherapeutics, Inc. Expansion de lymphocytes infiltrant les tumeurs avec des agonistes des canaux potassiques et leurs utilisations thérapeutiques
WO2018129332A1 (fr) 2017-01-06 2018-07-12 Iovance Biotherapeutics, Inc. Expansion de lymphocytes infiltrant les tumeurs (til) avec des agonistes de la superfamille des récepteurs du facteur de nécrose tumorale (tnfrsf) et des combinaisons thérapeutiques de til et d'agonistes de tnfrsf
US11357841B2 (en) 2017-01-06 2022-06-14 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes with potassium channel agonists and therapeutic uses thereof
US11618877B2 (en) 2017-01-13 2023-04-04 Instil Bio (Uk) Limited Aseptic tissue processing method, kit and device
US11618878B2 (en) 2017-01-13 2023-04-04 Instil Bio (Uk) Limited Aseptic tissue processing method, kit and device
US11549149B2 (en) 2017-01-24 2023-01-10 The Broad Institute, Inc. Compositions and methods for detecting a mutant variant of a polynucleotide
US11541077B2 (en) 2017-03-29 2023-01-03 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11254913B1 (en) 2017-03-29 2022-02-22 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10398734B2 (en) 2017-03-29 2019-09-03 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10925900B2 (en) 2017-03-29 2021-02-23 lovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10420799B2 (en) 2017-03-29 2019-09-24 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10933094B2 (en) 2017-03-29 2021-03-02 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
EP3722415A1 (fr) 2017-03-29 2020-10-14 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
US10946045B2 (en) 2017-03-29 2021-03-16 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10946044B2 (en) 2017-03-29 2021-03-16 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11344579B2 (en) 2017-03-29 2022-05-31 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10953046B2 (en) 2017-03-29 2021-03-23 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10695372B2 (en) 2017-03-29 2020-06-30 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10953047B2 (en) 2017-03-29 2021-03-23 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
TWI799402B (zh) * 2017-03-29 2023-04-21 美商艾歐凡斯生物治療公司 產生腫瘤浸潤淋巴球的方法及其在免疫治療中的應用
US11337998B2 (en) 2017-03-29 2022-05-24 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10363273B2 (en) 2017-03-29 2019-07-30 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
JP2020515257A (ja) * 2017-03-29 2020-05-28 アイオバンス バイオセラピューティクス，インコーポレイテッド 腫瘍浸潤リンパ球の製造方法及び免疫療法におけるその使用方法
US11529372B1 (en) 2017-03-29 2022-12-20 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10653723B1 (en) 2017-03-29 2020-05-19 Iovance, Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy
US11517592B1 (en) 2017-03-29 2022-12-06 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
JP7169291B2 (ja) 2017-03-29 2022-11-10 アイオバンス バイオセラピューティクス，インコーポレイテッド 腫瘍浸潤リンパ球の製造方法及び免疫療法におけるその使用方法
US11007226B2 (en) 2017-03-29 2021-05-18 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11007225B1 (en) 2017-03-29 2021-05-18 lovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10130659B2 (en) * 2017-03-29 2018-11-20 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10463697B2 (en) 2017-03-29 2019-11-05 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11013770B1 (en) 2017-03-29 2021-05-25 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10272113B2 (en) 2017-03-29 2019-04-30 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11304979B2 (en) 2017-03-29 2022-04-19 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
WO2018182817A1 (fr) 2017-03-29 2018-10-04 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
US11040070B2 (en) 2017-03-29 2021-06-22 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
EP3730608A1 (fr) 2017-03-29 2020-10-28 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
US11052115B2 (en) 2017-03-29 2021-07-06 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11052116B2 (en) 2017-03-29 2021-07-06 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11291687B2 (en) 2017-03-29 2022-04-05 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11273180B2 (en) 2017-03-29 2022-03-15 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11273181B2 (en) 2017-03-29 2022-03-15 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10646517B2 (en) 2017-03-29 2020-05-12 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11083752B2 (en) 2017-03-29 2021-08-10 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10918666B2 (en) 2017-03-29 2021-02-16 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10905718B2 (en) 2017-03-29 2021-02-02 lovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10639330B2 (en) 2017-03-29 2020-05-05 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11241456B2 (en) 2017-03-29 2022-02-08 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11202804B2 (en) 2017-03-29 2021-12-21 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11202803B1 (en) 2017-03-29 2021-12-21 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
EP3766964A1 (fr) 2017-03-29 2021-01-20 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
US10537595B2 (en) 2017-03-29 2020-01-21 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
EP4279574A3 (fr) * 2017-03-29 2024-04-10 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
CN110785486A (zh) * 2017-03-29 2020-02-11 艾欧凡斯生物治疗公司 肿瘤浸润淋巴细胞的生产方法及其在免疫治疗中的用途
EP3910055A1 (fr) 2017-03-29 2021-11-17 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
EP4279574A2 (fr) 2017-03-29 2023-11-22 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
US11939596B2 (en) 2017-03-29 2024-03-26 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10894063B2 (en) 2017-03-29 2021-01-19 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US10166257B2 (en) * 2017-03-29 2019-01-01 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11168304B2 (en) 2017-03-29 2021-11-09 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11168303B2 (en) 2017-03-29 2021-11-09 Iovance Biotherapeutics Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US20200246384A1 (en) * 2017-03-29 2020-08-06 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11898207B2 (en) 2017-03-31 2024-02-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Methods of isolating neoantigen-specific T cell receptor sequences
EP4234576A2 (fr) 2017-03-31 2023-08-30 The United States of America, as represented by the Secretary, Department of Health and Human Services Procédés d'isolement de séquences de récepteur de lymphocytes t spécifiques à un néo-antigène
WO2018183485A1 (fr) 2017-03-31 2018-10-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de séquences de récepteur de lymphocytes t spécifiques à un néo-antigène
US11963966B2 (en) 2017-03-31 2024-04-23 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating ovarian tumors
US11913075B2 (en) 2017-04-01 2024-02-27 The Broad Institute, Inc. Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer
WO2018191553A1 (fr) 2017-04-12 2018-10-18 Massachusetts Eye And Ear Infirmary Signature tumorale pour métastase, compositions de matière et leurs procédés d'utilisation
WO2018195019A1 (fr) 2017-04-18 2018-10-25 The Broad Institute Inc. Composition permettant de détecter une sécrétion et procédé d'utilisation
WO2018204761A1 (fr) * 2017-05-05 2018-11-08 H. Lee Moffitt Cancer Center And Research Institute, Inc. Procédé rapide de culture de lymphocytes infiltrant les tumeurs
WO2018209115A1 (fr) 2017-05-10 2018-11-15 Iovance Biotherapeutics, Inc. Expansion de lymphocytes infiltrant des tumeurs à partir de tumeurs liquides et leurs utilisations thérapeutiques
WO2020117233A1 (fr) 2017-06-05 2020-06-11 Iovance Biotherapeutics, Inc. Procédés d'utilisation de lymphocytes infiltrant les tumeurs dans un mélanome doublement réfractaire
US11433097B2 (en) * 2017-06-05 2022-09-06 Iovance Biotherapeutics, Inc. Methods of using tumor infiltrating lymphocytes in double-refractory melanoma
WO2018226714A1 (fr) 2017-06-05 2018-12-13 Iovance Biotherapeutics, Inc. Procédés d'utilisation de lymphocytes infiltrant les tumeurs dans un mélanome doublement réfractaire
US11819517B2 (en) 2017-06-05 2023-11-21 Iovance Biotherapeutics, Inc. Methods of using tumor infiltrating lymphocytes in double-refractory melanoma
US11897953B2 (en) 2017-06-14 2024-02-13 The Broad Institute, Inc. Compositions and methods targeting complement component 3 for inhibiting tumor growth
US10149898B2 (en) 2017-08-03 2018-12-11 Taiga Biotechnologies, Inc. Methods and compositions for the treatment of melanoma
EP4026554A1 (fr) 2017-08-03 2022-07-13 Taiga Biotechnologies, Inc. Procédés et compositions de traitement du mélanome
US10864259B2 (en) 2017-08-03 2020-12-15 Taiga Biotechnologies, Inc. Methods and compositions for the treatment of melanoma
WO2019027465A1 (fr) 2017-08-03 2019-02-07 Taiga Biotechnologies, Inc. Méthodes et compositions pharmaceutiques destinées au traitement du mélanome
CN107502589A (zh) * 2017-08-04 2017-12-22 北京世纪劲得生物技术有限公司 一种肿瘤浸润淋巴细胞与单个核细胞共培养方法
WO2019060336A1 (fr) 2017-09-20 2019-03-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Génération in vitro d'organoïde thymique à partir de cellules souches pluripotentes humaines
US11898166B2 (en) 2017-09-20 2024-02-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services In vitro generation of thymic organoid from human pluripotent stem cells
US11306132B2 (en) 2017-09-20 2022-04-19 The United States Of America, As Represented By The Secretary Department Of Health And Human Services HLA class II-restricted T cell receptors against mutated RAS
WO2019060349A1 (fr) 2017-09-20 2019-03-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t restreints au hla de classe ii contre kras muté
US11939365B2 (en) 2017-09-29 2024-03-26 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services T cell receptors recognizing mutated P53
WO2019067242A1 (fr) 2017-09-29 2019-04-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de cellules t ayant une spécificité antigénique pour une mutation spécifique du cancer p53
WO2019067243A1 (fr) 2017-09-29 2019-04-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t reconnaissant p53 mutée
WO2019070435A1 (fr) 2017-10-05 2019-04-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Méthodes d'expansion sélective de cellules exprimant un tcr avec une région constante murine
EP4269595A2 (fr) 2017-10-05 2023-11-01 The United States of America, as represented by the Secretary, Department of Health and Human Services Méthodes d'expansion sélective de cellules exprimant un tcr avec une région constante murine
WO2019075055A1 (fr) 2017-10-11 2019-04-18 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations de lymphocytes t au moyen d'inhibiteurs de mapk p38
WO2019077062A1 (fr) 2017-10-18 2019-04-25 Vivia Biotech, S.L. Cellules car-t activées par des bite
US11732257B2 (en) 2017-10-23 2023-08-22 Massachusetts Institute Of Technology Single cell sequencing libraries of genomic transcript regions of interest in proximity to barcodes, and genotyping of said libraries
WO2019094983A1 (fr) 2017-11-13 2019-05-16 The Broad Institute, Inc. Méthodes et compositions de traitement du cancer par ciblage de la voie clec2d-klrb1
WO2019100023A1 (fr) 2017-11-17 2019-05-23 Iovance Biotherapeutics, Inc. Expansion de til à partir de produits d'aspiration d'aiguille fine et de petites biopsies
WO2019103857A1 (fr) 2017-11-22 2019-05-31 Iovance Biotherapeutics, Inc. Expansion de lymphocytes de sang périphérique (pbl) à partir de sang périphérique
WO2019112932A1 (fr) 2017-12-04 2019-06-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Méthodes d'enrichissement de populations de cellules en lymphocytes t spécifiques du cancer à l'aide d'une stimulation in vitro de lymphocytes t mémoires
WO2019112941A1 (fr) 2017-12-04 2019-06-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t, limités à l'antigène hla de classe i, ayant une spécificité antigénique pour toute protéine ras mutée
US11466071B2 (en) 2017-12-04 2022-10-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services HLA class I-restricted t cell receptors against mutated RAS
WO2019118873A3 (fr) * 2017-12-15 2019-10-24 Iovance Biotherapeutics, Inc. Systèmes et procédés pour déterminer l'administration bénéfique de lymphocytes infiltrant les tumeurs et leurs procédés d'utilisation, et administration bénéfique de lymphocytes infiltrant les tumeurs et ses procédés d'utilisation
WO2019118873A2 (fr) 2017-12-15 2019-06-20 Iovance Biotherapeutics, Inc. Systèmes et procédés pour déterminer l'administration bénéfique de lymphocytes infiltrant les tumeurs et leurs procédés d'utilisation, et administration bénéfique de lymphocytes infiltrant les tumeurs et ses procédés d'utilisation
JP2021508104A (ja) * 2017-12-15 2021-02-25 アイオバンス バイオセラピューティクス，インコーポレイテッド 腫瘍浸潤リンパ球の有益な投与を決定するシステム及び方法並びにその使用方法、並びに腫瘍浸潤リンパ球の有益な投与及びその使用方法
WO2019136456A1 (fr) 2018-01-08 2019-07-11 Iovance Biotherapeutics, Inc. Procédés de génération de produits de til enrichis pour des lymphocytes t spécifiques d'un antigène tumoral
US11713446B2 (en) 2018-01-08 2023-08-01 Iovance Biotherapeutics, Inc. Processes for generating TIL products enriched for tumor antigen-specific T-cells
WO2019136459A1 (fr) 2018-01-08 2019-07-11 Iovance Biotherapeutics, Inc. Procédés de génération de produits de til enrichis pour des lymphocytes t spécifiques d'un antigène tumoral
US11834487B2 (en) 2018-02-12 2023-12-05 Hadasit Medical Research Services & Development Ltd. Modulation of SLAMF6 splice variants for cancer therapy
WO2019160829A1 (fr) 2018-02-13 2019-08-22 Iovance Biotherapeutics, Inc. Expansion de lymphocytes infiltrant les tumeurs (til) avec des antagonistes du récepteur a2a de l'adénosine et combinaisons thérapeutiques de til et d'antagonistes du récepteur a2a de l'adénosine
JP2021512962A (ja) * 2018-02-13 2021-05-20 アイオバンス バイオセラピューティクス，インコーポレイテッド アデノシンａ２ａ受容体アンタゴニストによる腫瘍浸潤性リンパ球（ｔｉｌ）の拡大培養並びにｔｉｌ及びアデノシンａ２ａ受容体アンタゴニストの治療的組み合わせ
WO2019173441A1 (fr) 2018-03-06 2019-09-12 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de préparation de populations de cellules et de réactifs rétroviraux pour l'immunothérapie cellulaire adoptive
WO2019190579A1 (fr) 2018-03-29 2019-10-03 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
CN112513254A (zh) * 2018-03-29 2021-03-16 艾欧凡斯生物治疗公司 肿瘤浸润淋巴细胞的制备方法及其在免疫治疗中的用途
WO2019209715A1 (fr) 2018-04-24 2019-10-31 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations de lymphocytes t faisant appel à de l'acide hydroxycitrique et/ou à un sel de celui-ci
US11957695B2 (en) 2018-04-26 2024-04-16 The Broad Institute, Inc. Methods and compositions targeting glucocorticoid signaling for modulating immune responses
US11384337B2 (en) 2018-04-27 2022-07-12 Iovance Biotherapeutics, Inc. Closed process for expansion and gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy
WO2019210131A1 (fr) 2018-04-27 2019-10-31 Iovance Biotherapeutics, Inc. Procédé en circuit fermé pour l'amplification et l'edition de gènes de lymphocytes d'infiltration des tumeurs et leurs utilisations en immunothérapie
CN112368003A (zh) * 2018-04-27 2021-02-12 艾欧凡斯生物治疗公司 肿瘤浸润淋巴细胞的基因编辑及其在免疫治疗中的用途
US11866688B2 (en) 2018-04-27 2024-01-09 Iovance Biotherapeutics, Inc. Closed process for expansion and gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy
WO2019213195A1 (fr) 2018-05-01 2019-11-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t reconnaissant un egfr muté
WO2019217753A1 (fr) 2018-05-10 2019-11-14 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2019232542A2 (fr) 2018-06-01 2019-12-05 Massachusetts Institute Of Technology Procédés et compositions pour détecter et moduler des signatures géniques micro-environnementales à partir du lcr de patients présentant des métastases
WO2020096682A2 (fr) 2018-08-31 2020-05-14 Iovance Biotherapeutics, Inc. Traitement de patients souffrant de nsclc réfractaires à un anticorps anti-pd-1
WO2020061429A1 (fr) 2018-09-20 2020-03-26 Iovance Biotherapeutics, Inc. Expansion de til à partir d'échantillons de tumeur cryoconservés
WO2020068816A1 (fr) * 2018-09-24 2020-04-02 H. Lee Moffitt Cancer Center And Research Institute, Inc. Culture de lymphocytes infiltrant les tumeurs issus d'une digestion de tumeur
WO2020072700A1 (fr) 2018-10-02 2020-04-09 Dana-Farber Cancer Institute, Inc. Lignées d'allèles uniques d'alh
WO2020081730A2 (fr) 2018-10-16 2020-04-23 Massachusetts Institute Of Technology Méthodes et compositions pour moduler un microenvironnement
WO2020086827A1 (fr) 2018-10-24 2020-04-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t restreints au hla-a3 dirigés contre une ras mutée
JP2022512915A (ja) * 2018-11-05 2022-02-07 アイオバンス バイオセラピューティクス，インコーポレイテッド 改良された腫瘍反応性ｔ細胞の選択
WO2020096989A1 (fr) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Traitement de patients souffrant de nsclc réfractaires à un anticorps anti-pd-1
WO2020096988A2 (fr) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2020096986A2 (fr) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Sélection de lymphocytes t réactifs à une tumeur améliorés
WO2020096927A1 (fr) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Expansion de til utilisant des inhibiteurs de la voie akt
WO2020131586A2 (fr) 2018-12-17 2020-06-25 The Broad Institute, Inc. Méthodes d'identification de néo-antigènes
WO2020131547A1 (fr) 2018-12-19 2020-06-25 Iovance Biotherapeutics, Inc. Procédés pour la multiplication de lymphocytes infiltrant les tumeurs à l'aide de paires de récepteurs de cytokines modifiés et leurs utilisations
US11739156B2 (en) 2019-01-06 2023-08-29 The Broad Institute, Inc. Massachusetts Institute of Technology Methods and compositions for overcoming immunosuppression
WO2020154275A1 (fr) 2019-01-22 2020-07-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe ii dirigés contre ras ayant une mutation g12r
WO2020172202A1 (fr) 2019-02-19 2020-08-27 Myst Therapeutics, Inc. Procédés de production de lymphocytes t autologues utilisés pour traiter les cancers, et compositions associées
WO2020186101A1 (fr) 2019-03-12 2020-09-17 The Broad Institute, Inc. Procédés de détection, compositions et méthodes de modulation des cellules de sarcome synovial
WO2020191079A1 (fr) 2019-03-18 2020-09-24 The Broad Institute, Inc. Compositions et méthodes de modulation de régulateurs métaboliques de pathogénicité de lymphocytes t
WO2020205662A1 (fr) 2019-03-29 2020-10-08 Myst Therapeutics, Inc. Procédés ex vivo de production d'un agent thérapeutique de lymphocytes t et compositions et procédés associés
WO2020232029A1 (fr) 2019-05-13 2020-11-19 Iovance Biotherapeutics, Inc. Procédés et compositions pour sélectionner des lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2020236967A1 (fr) 2019-05-20 2020-11-26 The Broad Institute, Inc. Mutant de délétion de crispr-cas aléatoire
WO2020243371A1 (fr) 2019-05-28 2020-12-03 Massachusetts Institute Of Technology Procédés et compositions pour la modulation de réponses immunitaires
WO2020264269A1 (fr) 2019-06-27 2020-12-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs des lymphocytes t reconnaissant la mutation r175h ou y220c dans p53
WO2021030627A1 (fr) 2019-08-13 2021-02-18 The General Hospital Corporation Procédés de prédiction de résultats d'inhibition de point de contrôle et traitement associés
WO2021041922A1 (fr) 2019-08-30 2021-03-04 The Broad Institute, Inc. Systèmes de transposase mu associés à crispr
WO2021055787A1 (fr) 2019-09-18 2021-03-25 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de populations de lymphocytes t
US11793787B2 (en) 2019-10-07 2023-10-24 The Broad Institute, Inc. Methods and compositions for enhancing anti-tumor immunity by targeting steroidogenesis
WO2021081378A1 (fr) 2019-10-25 2021-04-29 Iovance Biotherapeutics, Inc. Édition génique de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2021092555A2 (fr) 2019-11-08 2021-05-14 Kiyatec, Inc. Méthodes de criblage pour déterminer le dosage efficace d'agents thérapeutiques anticancéreux
WO2021108727A1 (fr) 2019-11-27 2021-06-03 Myst Therapeutics, Inc. Procédé de production d'une composition de lymphocytes t réactifs à une tumeur faisant appel à des agents modulateurs
WO2021118990A1 (fr) 2019-12-11 2021-06-17 Iovance Biotherapeutics, Inc. Procédés pour la production de lymphocytes infiltrant les tumeurs (til) et leurs procédés d'utilisation
US11767510B2 (en) 2019-12-20 2023-09-26 Instil Bio (Uk) Limited Devices and methods for isolating tumor infiltrating lymphocytes and uses thereof
US11865168B2 (en) 2019-12-30 2024-01-09 Massachusetts Institute Of Technology Compositions and methods for treating bacterial infections
WO2021142081A1 (fr) 2020-01-07 2021-07-15 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés de production de populations de lymphocytes t au moyen de cellules souches pluripotentes induites
WO2021163434A1 (fr) 2020-02-12 2021-08-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe i dirigés contre ras ayant une mutation g12d
WO2021163477A1 (fr) 2020-02-14 2021-08-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe ii dirigés contre ras ayant une mutation g12v
WO2021173902A1 (fr) 2020-02-26 2021-09-02 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe ii dirigés contre ras ayant une mutation g12v
WO2021174208A1 (fr) 2020-02-27 2021-09-02 Myst Therapeutics, Llc Procédés d'enrichissement et d'expansion ex vivo de lymphocytes t réactifs à une tumeur et compositions associées
WO2021188954A1 (fr) 2020-03-20 2021-09-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de lymphocytes t et de récepteurs de lymphocytes t à partir d'une tumeur par analyse de cellules uniques pour immunothérapie
WO2021188941A1 (fr) 2020-03-20 2021-09-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Procédés d'isolement de lymphocytes t et de récepteurs de lymphocytes t à partir de sang périphérique par analyse à une seule cellule pour l'immunothérapie
WO2021211455A1 (fr) 2020-04-13 2021-10-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe i contre lmp2
WO2021216920A1 (fr) 2020-04-22 2021-10-28 Iovance Biotherapeutics, Inc. Systèmes et procédés pour coordonner la fabrication de cellules pour l'immunothérapie spécifique au patient
US11631483B2 (en) 2020-04-22 2023-04-18 Iovance Biotherapeutics, Inc. Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy
WO2021226085A1 (fr) 2020-05-04 2021-11-11 Iovance Biotherapeutics, Inc. Sélection de lymphocytes t réactifs à une tumeur améliorés
WO2021226061A1 (fr) 2020-05-04 2021-11-11 Iovance Biotherapeutics, Inc. Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2021262829A2 (fr) 2020-06-24 2021-12-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t limités au hla de classe i contre le cd20
WO2022015694A1 (fr) 2020-07-13 2022-01-20 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe ii dirigés contre ras ayant une mutation g12d
WO2022015922A1 (fr) 2020-07-16 2022-01-20 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t drb à restriction hla de classe ii dirigés contre ras, comprenant une mutation g12v
WO2022051449A2 (fr) 2020-09-04 2022-03-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs des lymphocytes t reconnaissant les mutations r175h ou y220c dans p53
WO2022055946A1 (fr) 2020-09-08 2022-03-17 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Phénotypes de lymphocytes t associés à une réponse à une thérapie cellulaire adoptive
WO2022072760A1 (fr) 2020-10-02 2022-04-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe ii dirigés contre ras ayant une mutation g13d
US11981922B2 (en) 2020-10-05 2024-05-14 Dana-Farber Cancer Institute, Inc. Methods and compositions for the modulation of cell interactions and signaling in the tumor microenvironment
WO2022076606A1 (fr) 2020-10-06 2022-04-14 Iovance Biotherapeutics, Inc. Traitement de patients souffrant de cpnpc avec des thérapies de lymphocytes infiltrant les tumeurs
WO2022076952A1 (fr) 2020-10-06 2022-04-14 Iovance Biotherapeutics, Inc. Traitement de patients souffrant de cpnpc avec des thérapies lymphocytaires infiltrant les tumeurs
WO2022104035A2 (fr) 2020-11-13 2022-05-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Réactivité antigénique améliorée de cellules immunitaires exprimant une chaîne zêta cd3 de non-signalisation mutante
WO2022105816A1 (fr) * 2020-11-19 2022-05-27 苏州沙砾生物科技有限公司 Procédé de culture de lymphocytes infiltrant les tumeurs et son utilisation
WO2022125941A1 (fr) 2020-12-11 2022-06-16 Iovance Biotherapeutics, Inc. Traitement de patients atteints de cancer par des thérapies de lymphocytes infiltrant les tumeurs en combinaison avec des inhibiteurs de braf et/ou des inhibiteurs de mek
WO2022133140A1 (fr) 2020-12-17 2022-06-23 Iovance Biotherapeutics, Inc. Traitement avec des thérapies de lymphocytes infiltrant les tumeurs en combinaison avec des inhibiteurs de ctla-4 et de pd-1
WO2022133149A1 (fr) 2020-12-17 2022-06-23 Iovance Biotherapeutics, Inc. Traitement de cancers à l'aide de lymphocytes infiltrant les tumeurs
WO2022147196A2 (fr) 2020-12-31 2022-07-07 Iovance Biotherapeutics, Inc. Dispositifs et procédés de production automatisée de lymphocytes infiltrant les tumeurs
CN114763530A (zh) * 2021-01-15 2022-07-19 上海细胞治疗集团有限公司 一种诱导和制备til细胞的方法
WO2022170219A1 (fr) 2021-02-05 2022-08-11 Iovance Biotherapeutics, Inc. Traitement adjuvant du cancer
WO2022177961A1 (fr) 2021-02-16 2022-08-25 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe i contre cd22
WO2022187741A2 (fr) 2021-03-05 2022-09-09 Iovance Biotherapeutics, Inc. Stockage de tumeur et compositions de culture cellulaire
CN113005085A (zh) * 2021-03-18 2021-06-22 南方医科大学南方医院 一种新型的原发性肝癌肿瘤浸润淋巴细胞的培养及体外扩增方法
WO2022198141A1 (fr) 2021-03-19 2022-09-22 Iovance Biotherapeutics, Inc. Procédés pour la multiplication des lymphocytes infiltrant les tumeurs (til) liés à la sélection de cd39/cd69 et inactivation de gènes dans les til
WO2022204155A1 (fr) 2021-03-23 2022-09-29 Iovance Biotherapeutics, Inc. Édition génique cish de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie
WO2022204564A2 (fr) 2021-03-25 2022-09-29 Iovance Biotherapeutics, Inc. Procédés et compositions pour dosages de puissance de coculture de lymphocytes t et utilisation avec des produits de thérapie cellulaire
WO2022225981A2 (fr) 2021-04-19 2022-10-27 Iovance Biotherapeutics, Inc. Récepteurs costimulateurs chimériques, récepteurs de chimiokines et leur utilisation dans des immunothérapies cellulaires
WO2022225836A1 (fr) 2021-04-21 2022-10-27 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla de classe i dirigés contre ras ayant une mutation q61k
WO2022236050A1 (fr) 2021-05-07 2022-11-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t reconnaissant les mutations c135y, r175h, ou m237i dans p53
WO2022245754A1 (fr) 2021-05-17 2022-11-24 Iovance Biotherapeutics, Inc. Lymphocytes infiltrant les tumeurs modifiés par un gène pd-1 et leurs utilisations en immunothérapie
WO2023009716A1 (fr) 2021-07-28 2023-02-02 Iovance Biotherapeutics, Inc. Traitement de patients atteints d'un cancer avec des thérapies de lymphocytes infiltrant les tumeurs en combinaison avec des inhibiteurs de kras
WO2023039488A1 (fr) 2021-09-09 2023-03-16 Iovance Biotherapeutics, Inc. Procédés de production de produits til par inactivation de pd-1 avec talen
WO2023049862A1 (fr) 2021-09-24 2023-03-30 Iovance Biotherapeutics, Inc. Processus d'expansion et agents pour lymphocytes infiltrant la tumeur
WO2023077015A2 (fr) 2021-10-27 2023-05-04 Iovance Biotherapeutics, Inc. Systèmes et méthodes pour coordonner la fabrication de cellules pour l'immunothérapie spécifique d'un patient
WO2023086803A1 (fr) 2021-11-10 2023-05-19 Iovance Biotherapeutics, Inc. Procédés de traitement de multiplication utilisant des lymphocytes infiltrant les tumeurs cd8
WO2023102418A1 (fr) 2021-12-01 2023-06-08 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Récepteurs de lymphocytes t à restriction hla-a3 contre ras avec mutation g12v
WO2023137471A1 (fr) 2022-01-14 2023-07-20 Tune Therapeutics, Inc. Compositions, systèmes et procédés de programmation de phénotypes de lymphocytes t par activation génique ciblée
WO2023137472A2 (fr) 2022-01-14 2023-07-20 Tune Therapeutics, Inc. Compositions, systèmes et procédés de programmation de phénotypes de lymphocytes t par répression génique ciblée
WO2023147486A1 (fr) 2022-01-28 2023-08-03 Iovance Biotherapeutics, Inc. Lymphocytes infiltrant les tumeurs modifiés pour exprimer des charges utiles
WO2023196877A1 (fr) 2022-04-06 2023-10-12 Iovance Biotherapeutics, Inc. Traitement de patients souffrant de cpnpc avec des thérapies lymphocytaires infiltrant les tumeurs
WO2023201369A1 (fr) 2022-04-15 2023-10-19 Iovance Biotherapeutics, Inc. Processus d'expansion de til utilisant des combinaisons spécifiques de cytokine et/ou traitement akti
WO2023220608A1 (fr) 2022-05-10 2023-11-16 Iovance Biotherapeutics, Inc. Traitement de patients atteints d'un cancer avec des thérapies lymphocytaires infiltrant les tumeurs en combinaison avec un agoniste d'il-15r
WO2024011114A1 (fr) 2022-07-06 2024-01-11 Iovance Biotherapeutics, Inc. Dispositifs et procédés de production automatisée de lymphocytes infiltrant les tumeurs
WO2024030758A1 (fr) 2022-08-01 2024-02-08 Iovance Biotherapeutics, Inc. Récepteurs de costimulation chimériques, récepteurs de chimiokines et leur utilisation dans des immunothérapies cellulaires
WO2024055018A1 (fr) 2022-09-09 2024-03-14 Iovance Biotherapeutics, Inc. Procédés de génération de produits til à l'aide d'une double inactivation talen de pd-1/tigit
WO2024055017A1 (fr) 2022-09-09 2024-03-14 Iovance Biotherapeutics, Inc. Procédés de génération de produits til à l'aide d'une double inactivation de talen pd-1/tigit
WO2024064642A2 (fr) 2022-09-19 2024-03-28 Tune Therapeutics, Inc. Compositions, systèmes et méthodes de modulation de fonction de lymphocyte t
US11981921B2 (en) 2023-06-20 2024-05-14 Iovance Biotherapeutics, Inc. TIL expansion processes using specific cytokine combinations and/or AKTi treatment

Also Published As

Publication number Publication date
US11401503B2 (en) 2022-08-02
US20190345444A1 (en) 2019-11-14
WO2012129201A1 (fr) 2012-09-27
US20170152478A1 (en) 2017-06-01

Similar Documents

Publication Publication Date Title
US11401503B2 (en) Methods of growing tumor infiltrating lymphocytes in gas-permeable containers
US11905529B2 (en) Method of enhancing persistence of adoptively infused T cells
US11471486B2 (en) Selective and controlled expansion of educated NK cells
Jin et al. Simplified method of the growth of human tumor infiltrating lymphocytes in gas-permeable flasks to numbers needed for patient treatment
Prieto et al. Enrichment of CD8+ cells from melanoma tumor-infiltrating lymphocyte cultures reveals tumor reactivity for use in adoptive cell therapy
JP2023182601A (ja) 液性腫瘍からの腫瘍浸潤リンパ球の拡大培養及びその治療的使用
US20180223257A1 (en) Method for the induction and expansion of natural killer cells derived from peripheral blood mononuclear cells
AU2013379772B2 (en) Methods of producing enriched populations of tumor-reactive T cells from tumor
US20210052642A1 (en) Methods of enriching cell populations for cancer-specific t cells using in vitro stimulation of memory t cells
US20170073637A1 (en) Pooled nk cells from ombilical cord blood and their uses for the treatment of cancer and chronic infectious disease
CN107002029A (zh) 用于干细胞培养和治疗的诱导培养基和方法
Kerkar et al. Timing and intensity of exposure to interferon‐γ critically determines the function of monocyte‐derived dendritic cells
CN111902533A (zh) 产生自然杀伤细胞的方法
US20200017831A1 (en) Methods of preparing an isolated population of dendritic cells and methods of treating cancer using same
KR20230150833A (ko) 세포 배양 방법
US20210290672A1 (en) Regulation of tumor-associated t cells
AU2021381496A1 (en) Methods for culturing immune cells
Montagna et al. Single-cell cloning of human, donor-derived antileukemia T-cell lines for in vitro separation of graft-versus-leukemia effect from graft-versus-host reaction
US11753624B2 (en) Methods for generating functional therapeutic B cells ex-vivo
TWI837927B (zh) 生產富含幹細胞樣記憶ｔ細胞之人類嵌合抗原受體ｔ細胞的方法
WO2023147505A2 (fr) Procédé d'enrichissement de lymphocytes infiltrant les tumeurs
WO2023077034A1 (fr) Méthodes de culture de cellules immunitaires
JP2023538418A (ja) 腫瘍浸潤性リンパ球からの抗原特異的ＴＣＲを有するｉＰＳＣの優先的生成

Legal Events

Date Code Title Description
AS Assignment

Owner name: THE UNITED STATES OF AMERICA, AS REPRESENTED BY TH

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:ROSENBERG, STEVEN A.;DUDLEY, MARK E.;STRONCEK, DAVID;AND OTHERS;SIGNING DATES FROM 20120330 TO 20120405;REEL/FRAME:028011/0724

Owner name: WILSON WOLF MANUFACTURING CORPORATION, MINNESOTA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:ROSENBERG, STEVEN A.;DUDLEY, MARK E.;STRONCEK, DAVID;AND OTHERS;SIGNING DATES FROM 20120330 TO 20120405;REEL/FRAME:028011/0724

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION