WO2005084276A2 - Cell therapy formulation method and composition - Google Patents

Cell therapy formulation method and composition Download PDF

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Publication number
WO2005084276A2
WO2005084276A2 PCT/US2005/006446 US2005006446W WO2005084276A2 WO 2005084276 A2 WO2005084276 A2 WO 2005084276A2 US 2005006446 W US2005006446 W US 2005006446W WO 2005084276 A2 WO2005084276 A2 WO 2005084276A2
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cells
container
infusion
biodegradable
mixture
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PCT/US2005/006446
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French (fr)
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WO2005084276A3 (en
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Michael Har-Noy
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Immunovative Therapies, Ltd.
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Priority to PL05724065T priority Critical patent/PL1749090T3/en
Priority to EP05724065.7A priority patent/EP1749090B1/en
Priority to DK05724065.7T priority patent/DK1749090T3/en
Priority to CA2530514A priority patent/CA2530514C/en
Priority to ES05724065.7T priority patent/ES2635868T3/en
Priority to JP2007501882A priority patent/JP5144250B2/en
Publication of WO2005084276A2 publication Critical patent/WO2005084276A2/en
Priority to IL173405A priority patent/IL173405A/en
Publication of WO2005084276A3 publication Critical patent/WO2005084276A3/en
Priority to IL210244A priority patent/IL210244A0/en
Priority to IL223938A priority patent/IL223938B/en

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    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • 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
    • C12N2501/51—B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
    • 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
    • C12N2531/00—Microcarriers
    • 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
    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/30—Synthetic polymers
    • C12N2533/40—Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers

Definitions

  • FIELD OF INVENTION This invention relates to methods for formulating ex-vivo prepared T-cells for infusion. BACKGROUND OF THE INVENTION Cell therapy methods have been developed in order to enhance the host immune response to tumors, viruses and bacterial pathogens. Cell therapy methods often involve the ex-vivo activation and expansion of T-cells.
  • TIL tumor infiltrating lymphocyte
  • cytotoxic T-cells see U.S. Patent No. 6,255,073 issued to Cai, et al.; and U.S.
  • Patent No. 5,846,827 issued to Celis, et al. expanded tumor draining lymph node cells (see U.S. Patent No. 6,251,385 issued to Terman), and various other lymphocyte preparations (see U.S. Patent No. 6,194,207 issued to Bell, et al.;
  • T-cell formulations for infusion that maintain the cells in a state that can maximally orchestrate an immune response to cancer, infectious diseases and other disease states at both the time 6f infusion and while circulating in the blood.
  • Efforts to maintain the activation state of T- cells at the time of infusion have most commonly involved the formulation of the T-cells with exogenous IL-2.
  • Systemic IL-2 administration to patients has also been used to maintain the activation state of T-cells post-infusion.
  • exogenous IL-2 administration is extremely toxic to patients and has not resulted in significant benefit to patients undergoing T-cell infusions.
  • This invention includes ex-vivo prepared T-cells which are harvested from cell culture conditions and formulated in media suitable for infusion.
  • the method of formulation involves: (1) labeling the cells with one or more agents which have reactivity for T-cell surface moieties capable of delivering activation signals upon cross-linking; (2) mixing the labeled cells with biodegradable nanospheres or microspheres coated with a material capable of cross-linking the agents attached to the T-cell surface moieties; (3) suspending the mixture of labeled T-cells and coated biodegradable cross- linking spheres in a medium suitable for infusion; (4) packaging the mixture in a suitable container, such as a syringe or an IV infusion bag; and (5) parenteral administration of said mixture to a patient.
  • a suitable container such as a syringe or an IV infusion bag
  • the invention can be accomplished with a formulation method which involves: (1) mixing a population of T-cells with biodegradable nanospheres or microspheres coated with a first material and one or more second materials, whereas the first material binds the second materials and the second materials have reactivity for surface moieties on the T-cells, and whereas the interaction of the second materials with the T-cells causes the activation of the T-cells; (2) suspending the mixture of T-cells and the biodegradable spheres in a medium suitable for infusion; and (3) packaging the mixture in a suitable container, such as a syringe or an IV infusion bag; and (4) parenteral administration of the mixture to a patient.
  • a formulation method which involves: (1) mixing a population of T-cells with biodegradable nanospheres or microspheres coated with a first material and one or more second materials, whereas the first material binds the second materials and the second materials have reactivity for surface moieties on the T-cells, and whereas the
  • the T-cells intended for infusion are first harvested from the ex-vivo cell culture environment. The harvested cells are then either immediately formulated for infusion, cryopreserved for later formulation, or shipped to the patient location for formulation. Upon formulation by the method of the present invention, all the T-cells for infusion will be maximally activated in a non-toxic delivery vehicle.
  • all references to T-cells includes a population of cells with at least a portion of the cells containing T- cells.
  • T-cells are cells which express TCR, including ⁇ / ⁇ and ⁇ / ⁇ TCRs. T-cells include all cells which express CD3, including T-cell subsets which also express CD4 and CD8.
  • T-cells include both na ⁇ ve and memory cells and effector cells such as CTL. T-cells also include regulatory cells such as Thl, Tel, Th2, Tc2, Th3, Treg, and Trl cells. T-cells also include NKT-cells and similar unique classes of the T-cell lineage. PREFERRED EMBODIMENTS
  • the biodegradable spheres of the present invention are preferably manufactured from aliphatic polyesters, such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), copolymers of PLA and PGA (PLGA) or poly(carprolactone) (PCL), and polyanhydrides.
  • the spheres are produced into small particle sizes of 0.1 to 500 microns, preferably less than 10 microns and most preferably less than 1 micron. Microspheres of this size range are capable of direct injection into the body by conventional methods. It is preferred that the coated spheres be designed to degrade in physiological fluids within 7 days, more preferably within 3 days.
  • the preferred first material for coating on the biodegradable spheres is polyclonal goat (or sheep) anti-mouse polyclonal antibodies. By way of example, this preferred first material can be used to cross-link mouse-derived monoclonal antibodies, or fragments or genetically engineered derivatives thereof, that have specificity for T-cell ' surface moieties.
  • the mixing of goat anti-mouse coated microspheres (or nanospheres) with human T- cells labeled with mouse anti-human CD3 and mouse anti-human CD28 mAbs will cause the cross-linking of the mouse mAbs on the human T-cells through the binding of the goat anti-mouse polyclonal antibody with the mouse mAbs.
  • the cross-linking of the mAbs causes the activation of the T-cells.
  • the anti-human CD3 and anti-CD28 can also be first bound, preferably in a 50/50 ratio, on the goat (or sheep) polyclonal antibody coated spheres and mixed with the T-cells.
  • first materials and second materials can be used to accomplish the objective of cross-linking second agents attached to T-cell surface moieties in order to initiate signal transduction and activation of T-cells.
  • the mixture of T-cells with cross-linked surface moieties is suspended in infusion medium (e.g., isotonic solutions such as normal saline, 5% dextrose, Plasma-Lyte (Baxter) or Normasol (Abbott).
  • infusion medium e.g., isotonic solutions such as normal saline, 5% dextrose, Plasma-Lyte (Baxter) or Normasol (Abbott).
  • the infusion medium is supplemented with 0.5%-10% human serum albumen (HSA).
  • HSA human serum albumen
  • the mixture is preferably adjusted to a final T-cell concentration of between lx 10 to 1 x 10 cells per ml of infusion media.
  • 10 9 T-cells are formulated in 100 ml of infusion media.
  • the formulation is then packaged in one or more containers, such as syringes, plastic pouches, or plastic bottles.

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Abstract

Ex-vivo prepared T-cells are harvested from cell culture conditions and formulated in medium suitable for infusion. The formulation is made by labeling the cells with one or more agents which have reactivity for T-cell surface moieties capable of delivery activation signals upon cross-linking and mixing the labeled cells with biodegradable nanospheres or microspheres coated with a material capable of cross-linking the agents attached to the T-cell surface moieties. Alternatively, the formulation may be made by mixing a population of T-cells with biodegradable nanospheres or microspheres coated with a first material and one or more second materials. The first material binds the second material and the second material has reactivity for surface moieties on the T-cells and the interaction of the second materials with the T-cells causes the activation of the T-cells. In either method, the mixture of T-cells and biodegradable spheres are suspended in a medium suitable for infusion, and the mixture is packaged in a container.

Description

CELL THERAPY FORMULATION METHOD AND COMPOSITION
FIELD OF INVENTION This invention relates to methods for formulating ex-vivo prepared T-cells for infusion. BACKGROUND OF THE INVENTION Cell therapy methods have been developed in order to enhance the host immune response to tumors, viruses and bacterial pathogens. Cell therapy methods often involve the ex-vivo activation and expansion of T-cells.
Examples of these type of treatments include the use of tumor infiltrating lymphocyte (TIL) cells (see U.S. Patent No. 5,126,132 issued to Rosenberg), cytotoxic T-cells (see U.S. Patent No. 6,255,073 issued to Cai, et al.; and U.S.
Patent No. 5,846,827 issued to Celis, et al.), expanded tumor draining lymph node cells (see U.S. Patent No. 6,251,385 issued to Terman), and various other lymphocyte preparations (see U.S. Patent No. 6,194,207 issued to Bell, et al.;
U.S. Patent No. 5,443,983 issued to Ochoa, et al.; U.S. Patent No 6,040,177 issued to Riddell, et al.; U.S. Patent No. 5,766,920 issued to Babbitt, et al.). For maximum effectiveness of T-cells in cell therapy protocols, the ex vivo activated T-cell population should be in a state of maximal activation upon infusion. Efforts for developing improved methods for producing more effective T-cells for use in cell therapy protocols have focused on the ex-vivo activation methods. However, ex-vivo activated cells need to be harvested and administered to patients to have a therapeutic effect. The harvesting of the T-cells removes them from the activating stimuli available in the ex-vivo cultures. Therefore, the longer the time from harvest to infusion, the lower the quality of the T-cells. There is a need to develop T-cell formulations for infusion that maintain the cells in a state that can maximally orchestrate an immune response to cancer, infectious diseases and other disease states at both the time 6f infusion and while circulating in the blood. Efforts to maintain the activation state of T- cells at the time of infusion have most commonly involved the formulation of the T-cells with exogenous IL-2. Systemic IL-2 administration to patients has also been used to maintain the activation state of T-cells post-infusion. However, exogenous IL-2 administration is extremely toxic to patients and has not resulted in significant benefit to patients undergoing T-cell infusions. SUMMARY OF THE INVENTION This invention includes ex-vivo prepared T-cells which are harvested from cell culture conditions and formulated in media suitable for infusion. The method of formulation involves: (1) labeling the cells with one or more agents which have reactivity for T-cell surface moieties capable of delivering activation signals upon cross-linking; (2) mixing the labeled cells with biodegradable nanospheres or microspheres coated with a material capable of cross-linking the agents attached to the T-cell surface moieties; (3) suspending the mixture of labeled T-cells and coated biodegradable cross- linking spheres in a medium suitable for infusion; (4) packaging the mixture in a suitable container, such as a syringe or an IV infusion bag; and (5) parenteral administration of said mixture to a patient. Alternatively, the invention can be accomplished with a formulation method which involves: (1) mixing a population of T-cells with biodegradable nanospheres or microspheres coated with a first material and one or more second materials, whereas the first material binds the second materials and the second materials have reactivity for surface moieties on the T-cells, and whereas the interaction of the second materials with the T-cells causes the activation of the T-cells; (2) suspending the mixture of T-cells and the biodegradable spheres in a medium suitable for infusion; and (3) packaging the mixture in a suitable container, such as a syringe or an IV infusion bag; and (4) parenteral administration of the mixture to a patient. In practice ' of the present invention, the T-cells intended for infusion are first harvested from the ex-vivo cell culture environment. The harvested cells are then either immediately formulated for infusion, cryopreserved for later formulation, or shipped to the patient location for formulation. Upon formulation by the method of the present invention, all the T-cells for infusion will be maximally activated in a non-toxic delivery vehicle. For the purposes of the present invention, all references to T-cells includes a population of cells with at least a portion of the cells containing T- cells. T-cells are cells which express TCR, including α/β and γ/δ TCRs. T-cells include all cells which express CD3, including T-cell subsets which also express CD4 and CD8. T-cells include both naϊve and memory cells and effector cells such as CTL. T-cells also include regulatory cells such as Thl, Tel, Th2, Tc2, Th3, Treg, and Trl cells. T-cells also include NKT-cells and similar unique classes of the T-cell lineage. PREFERRED EMBODIMENTS The biodegradable spheres of the present invention are preferably manufactured from aliphatic polyesters, such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), copolymers of PLA and PGA (PLGA) or poly(carprolactone) (PCL), and polyanhydrides. The spheres are produced into small particle sizes of 0.1 to 500 microns, preferably less than 10 microns and most preferably less than 1 micron. Microspheres of this size range are capable of direct injection into the body by conventional methods. It is preferred that the coated spheres be designed to degrade in physiological fluids within 7 days, more preferably within 3 days. The preferred first material for coating on the biodegradable spheres is polyclonal goat (or sheep) anti-mouse polyclonal antibodies. By way of example, this preferred first material can be used to cross-link mouse-derived monoclonal antibodies, or fragments or genetically engineered derivatives thereof, that have specificity for T-cell 'surface moieties. Thus, for example, the mixing of goat anti-mouse coated microspheres (or nanospheres) with human T- cells labeled with mouse anti-human CD3 and mouse anti-human CD28 mAbs will cause the cross-linking of the mouse mAbs on the human T-cells through the binding of the goat anti-mouse polyclonal antibody with the mouse mAbs. The cross-linking of the mAbs causes the activation of the T-cells. Alternatively, the anti-human CD3 and anti-CD28 can also be first bound, preferably in a 50/50 ratio, on the goat (or sheep) polyclonal antibody coated spheres and mixed with the T-cells. It will be obvious to those skilled in the art that many combinations of first materials and second materials can be used to accomplish the objective of cross-linking second agents attached to T-cell surface moieties in order to initiate signal transduction and activation of T-cells. The mixture of T-cells with cross-linked surface moieties is suspended in infusion medium (e.g., isotonic solutions such as normal saline, 5% dextrose, Plasma-Lyte (Baxter) or Normasol (Abbott). In some embodiments, the infusion medium is supplemented with 0.5%-10% human serum albumen (HSA). The mixture is preferably adjusted to a final T-cell concentration of between lx 10 to 1 x 10 cells per ml of infusion media. In a preferred embodiment, 109 T-cells are formulated in 100 ml of infusion media. The formulation is then packaged in one or more containers, such as syringes, plastic pouches, or plastic bottles. Although the present invention has been described with reference to preferred embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention.

Claims

WHAT IS CLAIMED IS:
1. A composition comprising a treatment effective amount of cells, of which a portion are T-cells, whereby said T-cells are contacted with one or more first agents that ligate a cell surface moiety on at least a portion of the T- cells, and whereby the first agents are cross-linked by a second agent attached to a biodegradable support, and whereby said T-cells and biodegradable supports are suspended in a medium suitable for parenteral infusion and packaged in a suitable container.
2. The composition of claim 1 whereby the container is collapsible comprising opposing walls of flexible material and a flexible tube protruding from the container.
3. The composition of claim 1 whereby the container is a syringe.
4. A method for preparing a treatment effective amount of cells, of which a portion are T-cells, the method comprising: labeling the cells with one or more agents which have reactivity for T-cell surface moieties capable of delivering activation signals upon cross-linking; mixing the labeled cells with biodegradable nanospheres or microspheres coated with a material capable of cross- linking the agents attached to the T-cell surface moieties; suspending the mixture of labeled T-cells and coated biodegradable cross-linking spheres in a medium suitable for infusion; and packaging the mixture in a suitable container.
5. The method of claim 4 wherein the container is a syringe or an IN infusion bag.
6. The method of claim 4 wherein the container is collapsible.
7. The method of claim 6 wherein the container includes opposing walls of flexible material and an exit tube.
8. A method for preparing a treatment effective amount of cells, of which a portion are T-cells, the method comprising: mixing a population of T-cells with biodegradable nanospheres or microspheres coated with a first material and one or more second materials; whereas the first material binds the second materials, and the second materials have reactivity for surface moieties on the T-cells, and whereas the interaction of the second materials with the T-cells causes the activation of the T- cells; suspending the mixture of T-cells and the biodegradable spheres in a medium suitable for infusion; and packaging the mixture in a container;.
9. The method of claim 8 wherein the container is a syringe or an IN infusion bag.
10. The method of claim 8 wherein the container is collapsible.
11. The method of claim 10 wherein the container includes opposing walls of flexible material and an exit tube.
12. The method of claim 8 wherein the package mixture of the T-cell concentration is at least lx 107 cells per ml of infusion media.
PCT/US2005/006446 2004-03-01 2005-03-01 Cell therapy formulation method and composition WO2005084276A2 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
PL05724065T PL1749090T3 (en) 2004-03-01 2005-03-01 Cell therapy formulation method and composition
EP05724065.7A EP1749090B1 (en) 2004-03-01 2005-03-01 Cell therapy formulation method and composition
DK05724065.7T DK1749090T3 (en) 2004-03-01 2005-03-01 CELL THERAPY FORMULATION PROCEDURE AND COMPOSITION
CA2530514A CA2530514C (en) 2004-03-01 2005-03-01 Cell therapy formulation method and composition
ES05724065.7T ES2635868T3 (en) 2004-03-01 2005-03-01 Method and composition of cell therapy formulation
JP2007501882A JP5144250B2 (en) 2004-03-01 2005-03-01 Cell therapy formulation methods and compositions
IL173405A IL173405A (en) 2004-03-01 2006-01-29 Compositions for infusion containing ex-vivo prepared t-cells and methods for the preparation thereof
IL210244A IL210244A0 (en) 2004-03-01 2010-12-23 Compositions for infusion containing activated t- cells
IL223938A IL223938B (en) 2004-03-01 2012-12-27 Compositions for infusion containing ex-vivo prepared t-cells and methods for the preparation thereof

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US54903204P 2004-03-01 2004-03-01
US60/549,032 2004-03-01

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WO2005084276A3 WO2005084276A3 (en) 2007-05-10

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JP (3) JP5144250B2 (en)
CA (1) CA2530514C (en)
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ES (1) ES2635868T3 (en)
HU (1) HUE035726T2 (en)
IL (3) IL173405A (en)
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2089056A2 (en) * 2006-11-17 2009-08-19 Immunovative Therapies, Ltd. Biodegradable t-cell activation device and methods
US7956164B2 (en) 2004-02-26 2011-06-07 Immunovative Therapies Ltd. Device for enhancing immunostimulatory capabilities of T-cells
WO2015105999A1 (en) * 2014-01-08 2015-07-16 Immunovative Therapies, Ltd. Treatment of human immunodeficiency virus/acquired immunodeficiency syndrome
US9233156B2 (en) 2011-05-03 2016-01-12 Immunovative Therapies Ltd. Induction of IL-12 using immunotherapy
US10350242B2 (en) 2011-05-03 2019-07-16 Immunovative Therapies Ltd. Methods for handling biological drugs containing living cells

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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HUE035726T2 (en) 2018-05-28
IL223938B (en) 2020-01-30
IL173405A0 (en) 2006-06-11
JP5144250B2 (en) 2013-02-13
IL173405A (en) 2011-02-28
EP3202895A1 (en) 2017-08-09
WO2005084276A3 (en) 2007-05-10
PL1749090T3 (en) 2017-12-29
EP1749090A4 (en) 2009-04-29
CA2530514A1 (en) 2005-09-15
JP2007526314A (en) 2007-09-13
PT1749090T (en) 2017-08-28
JP2012021033A (en) 2012-02-02
JP2014077018A (en) 2014-05-01
JP5649551B2 (en) 2015-01-07
DK1749090T3 (en) 2017-09-04
IL210244A0 (en) 2011-03-31
EP1749090B1 (en) 2017-05-17
CA2530514C (en) 2017-01-31
ES2635868T3 (en) 2017-10-05

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