WO2023199069A1 - Récepteur antigénique chimérique qui se lie à la mésothéline - Google Patents

Récepteur antigénique chimérique qui se lie à la mésothéline Download PDF

Info

Publication number
WO2023199069A1
WO2023199069A1 PCT/GB2023/050998 GB2023050998W WO2023199069A1 WO 2023199069 A1 WO2023199069 A1 WO 2023199069A1 GB 2023050998 W GB2023050998 W GB 2023050998W WO 2023199069 A1 WO2023199069 A1 WO 2023199069A1
Authority
WO
WIPO (PCT)
Prior art keywords
cell
cells
car
domain
seq
Prior art date
Application number
PCT/GB2023/050998
Other languages
English (en)
Inventor
Gianpietro Dotti
Hongwei Du
Xin Zhou
Colette JOHNSTON
Original Assignee
Crescendo Biologics Limited
The University Of North Carolina At Chapel Hill
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 Crescendo Biologics Limited, The University Of North Carolina At Chapel Hill filed Critical Crescendo Biologics Limited
Publication of WO2023199069A1 publication Critical patent/WO2023199069A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • 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
    • A61K39/463—Cellular immunotherapy characterised by recombinant expression
    • A61K39/4631—Chimeric Antigen Receptors [CAR]
    • 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
    • A61K39/464402—Receptors, cell surface antigens or cell surface determinants
    • A61K39/464411—Immunoglobulin superfamily
    • A61K39/464412—CD19 or B4
    • 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
    • A61K39/464466—Adhesion molecules, e.g. NRCAM, EpCAM or cadherins
    • A61K39/464468—Mesothelin [MSLN]
    • 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
    • A61K39/464493—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; Prostatic acid phosphatase [PAP]; Prostate-specific G-protein-coupled receptor [PSGR]
    • A61K39/464495—Prostate specific membrane antigen [PSMA]
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35—Valency
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
    • C07K2319/43—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation containing a FLAG-tag
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • 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
    • C12N2510/00—Genetically modified cells

Definitions

  • the invention provides a cell or cell population or a pharmaceutical composition as above for use in therapy, e.g. for use in the treatment of cancer.
  • the invention provides a combination therapy comprising an effective amount of a cell or cell population or a pharmaceutical composition as above and an effective amount of an immune checkpoint inhibitor.
  • CDR refers to the complementarity-determining region within antibody variable sequences. There are three CDRs in each of the variable regions of the heavy chain and the light chain, which are designated CDR1 , CDR2 and CDR3, for each of the variable regions.
  • CDR set refers to a group of three CDRs that occur in a single variable region capable of binding the antigen. The exact boundaries of these CDRs have been defined differently according to different systems. The numbering system described by Kabat is used herein unless otherwise stated. Also, as used herein, the term VH or "variable domain” refers to immunoglobulin variable domains defined by Kabat et al.
  • MSLN binding molecule/protein/polypeptide/agent/moiety refers to a molecule capable of specifically binding to the human MSLN antigen.
  • the binding reaction may be shown by standard methods, for example with reference to a negative control test using an antibody of unrelated specificity. Binding is to human MSLN unless otherwise defined.
  • Yeast display technique are also included. This is further described in the examples.
  • Optimisation techniques known in the art such as display (e.g., ribosome and/or phage display) and I or mutagenesis (e.g., error-prone mutagenesis) can be used.
  • display e.g., ribosome and/or phage display
  • I or mutagenesis e.g., error-prone mutagenesis
  • sequence "homology” or “identity” generally refers to the percentage of amino acid residues in a sequence that are identical with the residues of the reference polypeptide with which it is compared, after aligning the sequences and in some embodiments after introducing gaps, if necessary, to achieve the maximum percent homology, and not considering any conservative substitutions as part of the sequence identity.
  • percent homology between two amino acid sequences is equivalent to the percent identity between the two sequences.
  • N- or C-terminal extensions, tags or insertions shall be construed as reducing identity or homology. Methods and computer programs for the alignment are well known.
  • the percent identity between two amino acid sequences can be determined using well known mathematical algorithms.
  • Epitopes formed from contiguous amino acids are typically, but not always, retained on exposure to denaturing solvents, whereas epitopes formed by tertiary folding are typically lost on treatment with denaturing solvents.
  • An epitope typically includes at least 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14 or 15 amino acids in a unique spatial conformation.
  • Methods for determining what epitopes are bound by a given antibody or antibody fragment i.e., epitope mapping
  • Methods for determining what epitopes are bound by a given antibody or antibody fragment include, for example, immunoblotting and immunoprecipitation assays, wherein overlapping or contiguous peptides from are tested for reactivity with a given antibody or antibody fragment. Competition assays can also be used to determine if a test antibody binds to the same epitope as a reference antibody.
  • the CAR of the invention further comprises a hinge or spacer region which connects the extracellular antigen binding domain and the transmembrane domain.
  • extracellular domains often comprise a hinge portion.
  • This hinge or spacer region can be used to achieve different lengths and flexibility of the resulting CAR.
  • Examples of the hinge or spacer region that can be used according to the invention include, but are not limited to, Fc fragments of antibodies or fragments or derivatives thereof, hinge regions of antibodies, or fragments or derivatives thereof, CH2 regions of antibodies, CH3 regions of antibodies, artificial spacer sequences, for example peptide sequences, or combinations thereof.
  • Other hinge or spacer region will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • the CAR may further include a label, for example a label that facilitates imaging, such as a fluorescent label or other tag. This can, for example, be used in methods for imaging tumor binding.
  • the label may be conjugated to the antigen binding domain.
  • the first target and the second target are not the same, i.e. are different targets, e.g., proteins; both may be present on a cell surface. Accordingly, a bispecific binding molecule as described herein can selectively and specifically bind to a cell that expresses (or displays on its cell surface) the first target (MSLN) and the second target (e.g. PSMA).
  • MSLN first target
  • PSMA second target
  • the binding molecule comprises more than two antigen-binding domains providing a multispecific binding molecule.
  • a multispecific antigen-binding domain as described herein can in addition to binding a first target (MSLN) bind one or more additional targets, i.e., a multispecific polypeptide can bind at least two, at least three, at least four, at least five, at least six, or more targets, wherein the multispecific polypeptide agent has at least two, at least, at least three, at least four, at least five, at least six, or more target binding sites respectively.
  • the bispecific antigen-binding domain has the following formula: VH (A)- L-VH (B) wherein A or B is MSLN.
  • V H (A) is conjugated to V H (B), i.e. linked to VH (B), for example with a peptide linker.
  • L denotes a linker for example a polypeptide linker.
  • peptide linker refers to a peptide comprising one or more amino acids.
  • a peptide linker comprises 1 to 44 amino acids, more particularly 2 to 20 amino acids.
  • Peptide linkers are known in the art or are described herein.
  • Suitable, non-immunogenic linker peptides are, for example, linkers that include G and/or S residues, (G4S)n, (SG4)n or G4(SG4)n peptide linkers, wherein "n” is generally a number between 1 and 10, e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9 or 10.
  • nucleic acid refers to deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), or a combination of a DNA or RNA.
  • RNA includes in vitro transcribed RNA or synthetic RNA; an mRNA sequence encoding a CAR polypeptide as described herein.
  • the nucleic acid may further comprise a suicide gene.
  • the construct may be in the form of a plasmid, vector, transcription or expression cassette.
  • a monoclonal antibody cocktail typically includes antibodies to CD14, CD20, GDI lb, CD16, HLA-DR, and CD8.
  • Flow cytometry and cell sorting may also be used to isolate cell populations of interest for use in the present invention.
  • PBMCs may be used directly for genetic modification with the immune cells (such as CARs or TCRs) using methods as described herein.
  • T lymphocytes after isolating the PBMCs, T lymphocytes can be further isolated and both cytotoxic and helper T lymphocytes can be sorted into naive, memory, and effector T cell subpopulations either before or after genetic modification and/or expansion.
  • the non-viral method includes the use of a transposon (also called a transposable element).
  • a transposon is a piece of DNA that can insert itself at a location in a genome, for example, a piece of DNA that is capable of self-replicating and inserting its copy into a genome, or a piece of DNA that can be spliced out of a longer nucleic acid and inserted into another place in a genome.
  • a transposon comprises a DNA sequence made up of inverted repeats flanking genes for transposition.
  • composition of the invention can be co-administered with other therapeutics, for example anti-cancer agents.
  • the invention relates to a method of making a population of cells as described herein, the method comprising:
  • In vitro cytotoxicity assay Tumor cells were seeded in 24-well plates at a concentration of 2.5x10 5 cells/well overnight. CAR-T cells were added to the plate at an E:T of 1 :5 without exogenous cytokines. Cocultures were analyzed 5-7 days following coculture to measure residual tumor cells and T cells by flow cytometry. Dead cells were recognized by Zombie Aqua Dye (Biolegend) staining while CAR-T cells were identified by CD3 staining and tumor cells by GFP. 26 CD69, PD-1 and Lag3 expression was measured by flow cytometry from day 0 to day 5 each day after coculture of CAR-T cells with tumor cells.
  • mice were infused 1 x 1 o 6 tumor cells per mice on clearance of the previous tumor.
  • T umor growth was monitored by bioluminescence using IVIS (In Vivo Imaging Systems)-Kinetics Optical in vivo imaging system (PerkinElmer) (PSMA-VH and MSLN-VH part) or AMI (AMI Medical Imaging) Optical in vivo imaging system (Spectral instruments imaging) (PSMA-VH/MSLN-VH part).
  • J591-T cells and PSMA-VH-T cells showed similar expansion in vitro when exposed to IL-15 and IL-7 cytokines, which was similar to CD19-T cells and NT-T cells (figure 1 D). Furthermore, no differences were observed in T cell composition as assessed by flow cytometry at day 12-14 of culture (figure 1 E).
  • proximal signaling of CAR-T cells before and after CAR cross-linking mediated by an anti-Flag Ab. Phosphorylation of the CAR-associated CD3 as well as phosphorylation of Akt and ERK were equal in J591-T cells and PSMA-VH-T cells (figure 1 F). Therefore, a VH domain-based CAR is expressed and signals in T cells on cross-linking as observed for scFv-based CAR-T cells.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Cell Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Microbiology (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oncology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Toxicology (AREA)
  • Reproductive Health (AREA)
  • Pregnancy & Childbirth (AREA)
  • Physics & Mathematics (AREA)
  • Gynecology & Obstetrics (AREA)
  • Plant Pathology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention concerne des récepteurs antigéniques chimériques (CAR) qui comprennent un anticorps à domaine variable humain unique qui se lie à la mésothéline humaine avec des séquences telles que définies dans la description. L'invention concerne également des cellules qui expriment de tels CAR.
PCT/GB2023/050998 2022-04-14 2023-04-13 Récepteur antigénique chimérique qui se lie à la mésothéline WO2023199069A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263330952P 2022-04-14 2022-04-14
US63/330,952 2022-04-14

Publications (1)

Publication Number Publication Date
WO2023199069A1 true WO2023199069A1 (fr) 2023-10-19

Family

ID=86185268

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2023/050998 WO2023199069A1 (fr) 2022-04-14 2023-04-13 Récepteur antigénique chimérique qui se lie à la mésothéline

Country Status (1)

Country Link
WO (1) WO2023199069A1 (fr)

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA16086A (fr) 1883-01-10 Edward J. Brooks Perfectionnements aux fermetures scellees pour assujetir les portes des chars et autres fins
CA193140A (fr) 1919-03-25 1919-10-14 William E. Kelly Moule a beton
WO2003000737A2 (fr) 2001-06-21 2003-01-03 The Babraham Institute Locus de la chaine legere $g(l) de souris
US20040043401A1 (en) 2002-05-28 2004-03-04 Sloan Kettering Institute For Cancer Research Chimeric T cell receotors
WO2004076618A2 (fr) 2003-02-26 2004-09-10 Babraham Institute Mammiferes non humains et cellules non humaines genetiquement modifies
WO2016062990A1 (fr) 2014-10-22 2016-04-28 Crescendo Biologics Limited Souris transgéniques
WO2017122017A1 (fr) 2016-01-12 2017-07-20 Crescendo Biologics Limited Molécules thérapeutiques
WO2017191476A1 (fr) 2016-05-06 2017-11-09 Crescendo Biologics Limited Récepteur antigénique chimérique à anticorps à domaine unique
WO2019012260A1 (fr) 2017-07-10 2019-01-17 Crescendo Biologics Limited Molécules thérapeutiques se liant à psma
WO2019200007A1 (fr) 2018-04-10 2019-10-17 Amgen Inc. Récepteurs chimères pour dll3 et leurs procédés d'utilisation
WO2021108613A1 (fr) 2019-11-26 2021-06-03 Novartis Ag Récepteurs antigéniques chimériques pour cd19 et cd22 et leurs utilisations
WO2022262859A1 (fr) * 2021-06-18 2022-12-22 江苏先声药业有限公司 Anticorps humanisé anti-msln humain et son utilisation

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA16086A (fr) 1883-01-10 Edward J. Brooks Perfectionnements aux fermetures scellees pour assujetir les portes des chars et autres fins
CA193140A (fr) 1919-03-25 1919-10-14 William E. Kelly Moule a beton
WO2003000737A2 (fr) 2001-06-21 2003-01-03 The Babraham Institute Locus de la chaine legere $g(l) de souris
US20040043401A1 (en) 2002-05-28 2004-03-04 Sloan Kettering Institute For Cancer Research Chimeric T cell receotors
WO2004076618A2 (fr) 2003-02-26 2004-09-10 Babraham Institute Mammiferes non humains et cellules non humaines genetiquement modifies
WO2016062990A1 (fr) 2014-10-22 2016-04-28 Crescendo Biologics Limited Souris transgéniques
WO2017122017A1 (fr) 2016-01-12 2017-07-20 Crescendo Biologics Limited Molécules thérapeutiques
WO2017191476A1 (fr) 2016-05-06 2017-11-09 Crescendo Biologics Limited Récepteur antigénique chimérique à anticorps à domaine unique
WO2019012260A1 (fr) 2017-07-10 2019-01-17 Crescendo Biologics Limited Molécules thérapeutiques se liant à psma
WO2019200007A1 (fr) 2018-04-10 2019-10-17 Amgen Inc. Récepteurs chimères pour dll3 et leurs procédés d'utilisation
WO2021108613A1 (fr) 2019-11-26 2021-06-03 Novartis Ag Récepteurs antigéniques chimériques pour cd19 et cd22 et leurs utilisations
WO2022262859A1 (fr) * 2021-06-18 2022-12-22 江苏先声药业有限公司 Anticorps humanisé anti-msln humain et son utilisation

Non-Patent Citations (52)

* Cited by examiner, † Cited by third party
Title
"GenBank", Database accession no. AAA62478.2
AHMAD ZAYEAP SKALI AM ET AL.: "scFv antibody: principles and clinical application", CLIN DEV IMMUNOL, vol. 2012, 2012, pages 1 - 15, XP055549405, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/22474489> DOI: 10.1155/2012/980250
AHN SLI JSUN C ET AL.: "Cancer immunotherapy with T cells carrying bispecific receptors that mimic antibodies", CANCER IMMUNOL RES, vol. 7, 2019, pages 773 - 83, XP055772069, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/30842091> DOI: 10.1158/2326-6066.CIR-18-0636
BARBER AZHANG TDEMARS LR ET AL.: "Chimeric NKG2D receptor-bearing T cells as immunotherapy for ovarian cancer", CANCER RES, vol. 67, 2007, pages 5003 - 8, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/17510432>
BOLLARD CMTRIPIC TCRUZ CR ET AL.: "Tumor-Specific T-cells engineered to overcome tumor immune evasion induce clinical responses in patients with relapsed Hodgkin lymphoma", J CLIN ONCOL, vol. 36, 2018, pages 1128 - 39, XP009528705, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/29315015> DOI: 10.1200/JCO.2017.74.3179
BROWN CEALIZADEH DSTARR R ET AL.: "Regression of glioblastoma after chimeric antigen receptor T-cell therapy", N ENGL J MED, vol. 375, 2016, pages 2561 - 9, XP055564981, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/28029927> DOI: 10.1056/NEJMoa1610497
BRUSCHI, C.V.GJURACIC, K.: "Encyclopedia of Life Sciences", 2002, MACMILLAN PUBLISHERS LTD., article "Yeast Artificial Chromosomes"
CHANG SS: "Overview of prostate-specific membrane antigen", REV UROL, vol. 6, 2004, pages S13 - 18, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/16985927>
DIACONU IBALLARD BZHANG M ET AL.: "Inducible caspase-9 selectively modulates the toxicities of CD19-specific chimeric antigen receptor-modified T cells", MOL THER, vol. 25, 2017, pages 580 - 92, XP055692323, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/28187946> DOI: 10.1016/j.ymthe.2017.01.011
DOTTI GGOTTSCHALK SSAVOLDO B ET AL.: "Design and development of therapies using chimeric antigen receptor-expressing T cells", IMMUNOL REV, vol. 257, 2014, pages 107 - 26, XP055552726, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/24329793> DOI: 10.1111/imr.12131
DU HHIRABAYASHI KAHN S ET AL.: "Antitumor responses in the absence of toxicity in solid tumors by targeting B7-H3 via chimeric antigen receptor T cells", CANCER CELL, vol. 35, 2019, pages 221 - 37, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/30753824>
ESHHAR ZWAKS TGROSS G ET AL.: "Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors", PROC NATL ACAD SCI USA, vol. 90, 1993, pages 720 - 4, XP002009770, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/8421711> DOI: 10.1073/pnas.90.2.720
FINNEY HMLAWSON ADBEBBINGTON CR ET AL.: "Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product", J IMMUNOL, vol. 161, 1998, pages 2791 - 7, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/9743337>
FUCA GREPPEL LLANDONI E ET AL.: "Enhancing chimeric antigen receptor T-cell efficacy in solid tumors", CLIN CANCER RES, vol. 26, 2020, pages 2444 - 51, XP055967810, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/32015021> DOI: 10.1158/1078-0432.CCR-19-1835
HAMERS-CASTERMAN CATARHOUCH TMUYLDERMANS S ET AL.: "Naturally occurring antibodies devoid of light chains", NATURE, vol. 363, 1993, pages 446 - 8, XP002535892, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/8502296> DOI: 10.1038/363446a0
HECZEY ALOUIS CUSAVOLDO B ET AL.: "Car T cells administered in combination with Lymphodepletion and PD-1 inhibition to patients with neuroblastoma", MOL THER, vol. 25, 2017, pages 2214 - 24, XP093008964, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/28602436> DOI: 10.1016/j.ymthe.2017.05.012
HOLLIGER PHUDSON PJ: "Engineered antibody fragments and the rise of single domains", NAT BIOTECHNOL, vol. 23, 2005, pages 1126 - 36, XP008076746, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/16151406> DOI: 10.1038/nbt1142
HONG LKCHEN YSMITH CC ET AL.: "CD30-Redirected Chimeric Antigen Receptor T Cells Target CD30+ and CD30- Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions", CANCER IMMUNOL RES, vol. 6, 2018, pages 1274 - 87, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/30087115>
IMAI CMIHARA KANDREANSKY M ET AL.: "Chimeric receptors with 4-1 BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia", LEUKEMIA, vol. 18, 2004, pages 676 - 84, XP037781725, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/14961035> DOI: 10.1038/sj.leu.2403302
JAMNANI FRRAHBARIZADEH FSHOKRGOZAR MA ET AL.: "T cells expressing VHH-directed oligoclonal chimeric HER2 antigen receptors: towards tumor-directed oligoclonal T cell therapy", BIOCHIM BIOPHYS ACTA, vol. 1840, 2014, pages 378 - 86, XP055108962, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/24076235> DOI: 10.1016/j.bbagen.2013.09.029
KABAT ET AL., ANN. NY ACAD. SCI., vol. 190, 1971, pages 382 - 391
KABAT ET AL.: "Sequences of Proteins of Immunological Interest", 1991, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
LAM NTRINKLEIN NDBUELOW B ET AL.: "Anti-BCMA chimeric antigen receptors with fully human heavy-chain-only antigen recognition domains", NAT COMMUN, vol. 11, 2020, pages 283, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/31941907>
LANDONI EFUCA GWANG J ET AL.: "Modifications to the framework regions eliminate chimeric antigen receptor tonic signaling", CANCER IMMUNOL RES, 5 February 2021 (2021-02-05), Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/33547226>
LV JZHAO RWU D ET AL.: "Mesothelin is a target of chimeric antigen receptor T cells for treating gastric cancer", J HEMATOL ONCOL, vol. 12, 2019, pages 18, XP055727450, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/30777106> DOI: 10.1186/s13045-019-0704-y
MA XSHOU PSMITH C ET AL.: "Interleukin-23 engineering improves CAR T cell function in solid tumors", NAT BIOTECHNOL, vol. 38, 2020, pages 448 - 59, XP037086863, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/32015548> DOI: 10.1038/s41587-019-0398-2
MILLER BRDEMAREST SJLUGOVSKOY A ET AL.: "Stability engineering of scFvs for the development of bispecific and multivalent antibodies", PROTEIN ENG DES SEL, vol. 23, 2010, pages 549 - 57, XP002690428, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/20457695> DOI: 10.1093/protein/gzq028
MORELLO ASADELAIN MADUSUMILLI PS: "Mesothelin-Targeted cars: driving T cells to solid tumors", CANCER DISCOV, vol. 6, 2016, pages 133 - 46, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/26503962>
O'ROURKE DMNASRALLAH MPDESAI A ET AL.: "A single dose of peripherally infused EGFRvlll-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma", SCI TRANSL MED, vol. 9, 2017, pages eaaa0984, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/28724573>
PARK SSHEVLIN EVEDVYAS Y ET AL.: "Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity", SCI REP, vol. 7, 2017, pages 14366, XP055656078, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/29085043> DOI: 10.1038/s41598-017-14749-3
RAJABZADEH ARAHBARIZADEH FAHMADVAND D ET AL.: "A VHH-Based anti-MUC1 chimeric antigen receptor for specific retargeting of human primary T cells to MUC1-positive cancer cells", CELL J, vol. 22, 2021, pages 502 - 13, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/32347044>
RAMOS CAGROVER NSBEAVEN AW ET AL.: "Anti-Cd30 CAR-T cell therapy in relapsed and refractory Hodgkin lymphoma", J CLIN ONCOL, vol. 38, 2020, pages 3794 - 804, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/32701411>
REN ET AL., GENOMICS, vol. 84, 2004, pages 686
RICHMAN SANUNEZ-CRUZ SMOGHIMI B ET AL.: "High-Affinity GD2-Specific CAR T cells induce fatal encephalitis in a preclinical neuroblastoma model", CANCER IMMUNOL RES, vol. 6, 2018, pages 36,46, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/29180536>
SADELAIN ET AL., CURR OPIN IMMUNOL, vol. 21, no. 2, 2009, pages 215 - 223
SADELAIN MBRENTJENS RRIVIERE I: "The basic principles of chimeric antigen receptor design", CANCER DISCOV, vol. 3, 2013, pages 388 - 98, XP055287277, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/23550147> DOI: 10.1158/2159-8290.CD-12-0548
SAMPSON JHGUNN MDFECCI PE ET AL.: "Brain immunology and immunotherapy in brain tumours", NAT REV CANCER, vol. 20, 2020, pages 12 - 25, XP036974944, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/31806885> DOI: 10.1038/s41568-019-0224-7
SHAFFER DRSAVOLDO BYI Z ET AL.: "T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies", BLOOD, vol. 117, 2011, pages 4304 - 14, XP002738263, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/21304103> DOI: 10.1182/blood-2010-04-278218
SHAH NNFRY TJ: "Mechanisms of resistance to CAR T cell therapy", NAT REV CLIN ONCOL, vol. 3, 2019, pages 372 - 85, XP036789414, DOI: 10.1038/s41571-019-0184-6
SHARIFZADEH ZRAHBARIZADEH FSHOKRGOZAR MA ET AL.: "Genetically engineered T cells bearing chimeric nanoconstructed receptors harboring TAG-72-specific camelid single domain antibodies as targeting agents", CANCER LETT, vol. 334, 2013, pages 237 - 44, XP028555132, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/22902507> DOI: 10.1016/j.canlet.2012.08.010
STANFIELD RLDOOLEY HFLAJNIK MF ET AL.: "Crystal structure of a shark single-domain antibody V region in complex with lysozyme", SCIENCE, vol. 305, 2004, pages 1770 - 3, XP002989770, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/15319492> DOI: 10.1126/science.1101148
STERNER, R.C.STERNER, R.M: "CAR-T cell therapy: current limitations and potential strategies", BLOOD CANCER J., vol. 11, 2021, pages 69
TENG YUMIN ET AL: "Diverse human VH antibody fragments with bio-therapeutic properties from the Crescendo Mouse", NEW BIOTECHNOLOGY, ELSEVIER BV, NL, vol. 55, 7 October 2019 (2019-10-07), pages 65 - 76, XP086034492, ISSN: 1871-6784, [retrieved on 20191007], DOI: 10.1016/J.NBT.2019.10.003 *
TENG YYOUNG JLEDWARDS B ET AL.: "Diverse human VH antibody fragments with bio-therapeutic properties from the Crescendo Mouse", N BIOTECHNOL, vol. 55, 2020, pages 65 - 76, XP086034492, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/31600579> DOI: 10.1016/j.nbt.2019.10.003
WANG DSHAO YZHANG X ET AL.: "11-23 and PSMA-targeted duo-CAR T cells in prostate cancer eradication in a preclinical model", J TRANSL MED, vol. 18, 2020, pages 23, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/31937346>
WANG GUANMENG ET AL: "Fully human antibody V H domains to generate mono and bispecific CAR to target solid tumors", JOURNAL FOR IMMUNOTHERAPY OF CANCER, vol. 9, no. 4, 1 April 2021 (2021-04-01), pages e002173, XP093054299, DOI: 10.1136/jitc-2020-002173 *
WANG QCHEN YPARK J ET AL.: "Design and production of bispecific antibodies", ANTIBODIES, vol. 8, 2019, pages 43
WATANABE KTERAKURA SUCHIYAMA S ET AL.: "Excessively high-affinity single-chain fragment variable region in a chimeric antigen receptor can counteract T-cell proliferation", BLOOD, vol. 124, 2014, pages 4799, XP086740002, DOI: 10.1182/blood.V124.21.4799.4799
XIONG WCHEN YKANG X ET AL.: "Immunological synapse predicts effectiveness of chimeric antigen receptor cells", MOL THER, vol. 26, 2018, pages 963 - 75, XP055525745, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/29503199> DOI: 10.1016/j.ymthe.2018.01.020
YU HPAN JGUO Z ET AL.: "Cart cell therapy for prostate cancer: status and promise", ONCO TARGETS THER, vol. 12, 2019, pages 391 - 5, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/30655675>
ZHANG ZJIANG DYANG H ET AL.: "Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor", CELL DEATH DIS, vol. 10, 2019, pages 476, XP055727451, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/31209210> DOI: 10.1038/s41419-019-1711-1
ZOU ET AL., J. IMMUNOL., vol. 170, 2003, pages 1354

Similar Documents

Publication Publication Date Title
JP7402933B2 (ja) 導入遺伝子の遺伝子タグおよびその使用方法
US11866510B2 (en) Chimeric antigen receptor with single domain antibody
CN109715808A (zh) 用于选择性蛋白质表达的组合物和方法
WO2021136263A1 (fr) Cellule effectrice immunitaire modifiée et son procédé de préparation
CN112979828A (zh) 靶向cld18a2的t淋巴细胞及其制备方法和应用
KR20200000495A (ko) 키메라 항원 수용체 단백질을 코딩하는 핵산 및 키메라 항원 수용체 단백질을 발현하는 t 림프구
US11999773B2 (en) Anti-BCMA chimeric antigen receptors
CN111909271B (zh) 一种基于单域抗体的bcma嵌合抗原受体及其应用
CN115916833B (zh) 靶向b7h3的抗原结合多肽及其应用
CN112739721B (zh) 一种单域抗体及包含抗体结构的嵌合抗原受体
WO2023093811A1 (fr) Combinaison d&#39;une cellule de récepteur antigénique chimérique de type à régulation de commutation moléculaire et d&#39;un anticorps, et son utilisation
EP4257617A1 (fr) Protéine de liaison à l&#39;antigène ciblant cd70 et son utilisation
CN117229407B (zh) 一种靶向gprc5d的单域抗体、嵌合抗原受体及其应用
EP3946435B1 (fr) Amélioration de l&#39;activité des lymphocytes t cytolytiques par inhibition ebag9
CN117986362A (zh) 靶向b7h3的通用型car-t细胞及其制备方法和应用
CN116284389A (zh) 抗afp/hla02 tcr样抗体及其用途
WO2023199069A1 (fr) Récepteur antigénique chimérique qui se lie à la mésothéline
WO2023199068A1 (fr) Liants à base de mésothéline
WO2023274380A1 (fr) LYMPHOCYTE CAR-T UNIVERSEL CIBLANT IL13Rα2, SON PROCÉDÉ DE PRÉPARATION ET SON APPLICATION
WO2023273762A1 (fr) Épitope conformationnel spatial induisant une rétention efficace de cd3 dans des cellules et son utilisation
WO2023274387A1 (fr) Cellule car-t universelle ciblant le gd2, son procédé de préparation et son application
WO2020241827A1 (fr) Cellules exprimant un récepteur antigénique chimérique pour cibler la kinase alk
CN118206661A (zh) 一种靶向间皮素的单域抗体、嵌合抗原受体及其应用
CN116410332A (zh) 抗间皮素纳米抗体嵌合抗原受体及其应用
CN118271440A (zh) 靶向IL13Rα2的抗体以及靶向IL13Rα2的免疫效应细胞

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23719451

Country of ref document: EP

Kind code of ref document: A1