NZ805217A - Novel engineered t cell receptors and immune therapy using the same - Google Patents

Novel engineered t cell receptors and immune therapy using the same

Info

Publication number
NZ805217A
NZ805217A NZ805217A NZ80521718A NZ805217A NZ 805217 A NZ805217 A NZ 805217A NZ 805217 A NZ805217 A NZ 805217A NZ 80521718 A NZ80521718 A NZ 80521718A NZ 805217 A NZ805217 A NZ 805217A
Authority
NZ
New Zealand
Prior art keywords
antigen recognizing
recognizing construct
seq
col6a3
host cell
Prior art date
Application number
NZ805217A
Inventor
Claudia Wagner
Dominik Maurer
Leonie Alten
Sebastian Bunk
Felix Unverdorben
Martin Hofmann
Meike Hutt
Original Assignee
Immatics Biotechnologies Gmbh
Filing date
Publication date
Application filed by Immatics Biotechnologies Gmbh filed Critical Immatics Biotechnologies Gmbh
Publication of NZ805217A publication Critical patent/NZ805217A/en

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Abstract

The present invention pertains to antigen recognizing constructs against COL6A3 antigens. The invention in particular provides novel engineered T cell receptor (TCR) based molecules which are selective and specific for the tumor expressing antigen COL6A3. The TCR of the invention, and COL6A3 antigen binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of COL6A3 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Claims (1)

  1. Claims 5. An antigen recognizing construct comprising a first domain and a second domain, each domain comprising three complementary determining regions (CDRs), wherein the first domain comprises the amino acid sequences according to SEQ ID NOs: 6 (CDRa2) and 7 (CDRa3), and the second domain comprises the amino acid sequences according to SEQ ID NOs: 14 (CDRb2) and 15 (CDRb3), wherein (a) (b) the CDRa1 of the first domain is as set forth in SEQ ID NO: 26 and the CDRb1 of the second domain is as set forth in SEQ ID NO: 40, and wherein the antigen recognizing construct comprises the sequence as set forth in SEQ ID NO:65, or the sequences as set forth in SEQ ID NOs: 62 and 63; or the CDRa1 of the first domain is as set forth in SEQ ID NO: 5 and the CDRb1 of the second domain is as set forth in SEQ ID NO: 40, and wherein the antigen recognizing construct comprises the sequence as set forth in SEQ ID NO:64, or the sequences as set forth in SEQ ID NOs: 62 and 2. The antigen recognizing construct according to claim 1, wherein said antigen recognizing construct is stable, and capable of specifically and/or selectively binding to a COL6A3 antigenic peptide comprising the amino acid sequence according to SEQ ID NO: 1, in the context with MHC. The antigen recognizing construct according to claim 1 or 2, wherein the antigen recognizing construct is a T cell receptor (TCR) or derivative or fragment thereof, wherein the derivative or fragment retains the antigen binding and/or recognizing ability of the molecule to specifically and/or selectively bind to COL6A3 antigenic polypeptide. The antigen recognizing construct according to any one of claims 1 to 3, wherein said first domain is part of a TCR α or γ chain; and/or wherein said second domain is part of a TCR β or δ chain. The antigen recognizing construct according to any one of claims 1 to 4, wherein the antigen recognizing construct is a single chain antigen recognizing construct, preferably wherein the single chain antigen recognizing construct is a single chain TCR. 43 13. The antigen recognizing construct according to any one of claims 1 to 5, wherein the antigen recognizing construct is a soluble TCR. The antigen recognizing construct according to claim 6, wherein the soluble TCR is a heterodimeric truncated TCR variant comprising at least (a) the variable domains of the TCR α-chain of SEQ ID NO:62 and β-chain of SEQ ID NO:63; or (b) the variable domains of the TCR α-chain of SEQ ID NO:62 and β-chain of SEQ ID NO:2; linked by a polypeptide linker having a sequence selected from the group consisting of SEQ ID NOs:22, 24, 25 and 27. A nucleic acid or nucleic acids encoding for an antigen recognizing construct according to any one of claims 1 to 7. A nucleic acid vector or nucleic acid vectors comprising the nucleic acid of claim 8. A recombinant host cell comprising an antigen recognizing construct according to any one of claims 1 to 7, the nucleic acid of claim 8 or the vector according to claim 9, wherein said host cell preferably is a mammalian cell, more preferably a human cell. The host cell according to claim 10, wherein said host cell is a) a lymphocyte, preferably a T lymphocyte or T lymphocyte progenitor cell, more preferably a CD4 or CD8 positive T cell, or b) a non-lymphocyte. A pharmaceutical composition comprising the antigen recognizing construct according to any one of claims 1 to 7, the nucleic acid according to claim 8, the vector according to claim 9, or the recombinant host cell according to claim 10 or 11, and a pharmaceutically acceptable carrier, diluent stabilizer and/or excipient. A method of producing the COL6A3-specific antigen recognizing construct according to any one of claims 1 to 7, comprising a. providing a suitable host cell, 44 b. c. d. 14. providing a genetic construct comprising a coding sequence encoding the antigen recognizing construct according to claim 1, introducing said genetic construct into said suitable host cell, and expressing said genetic construct by said suitable host cell, the method preferably further comprising isolating and purifying the antigen recognizing construct from the suitable host cell and, optionally, reconstituting the antigen recognizing construct in a T-cell. Use of the antigen recognizing construct according to any one of claims 1 to 7, the nucleic acid according to claim 8, the vector according to claim 9, the host cell according to claim 10 or 11 or the pharmaceutical composition according to claim 12, for the manufacture of a medicament. 18. Use of the antigen recognizing construct according to any one of claims 1 to 7, the nucleic acid according to claim 8, the vector according to claim 9, the host cell according to claim 10 or 11, or the pharmaceutical composition according to claim 12 for the manufacture of a medicament for the diagnosis, prevention, and/or treatment of a proliferative disease. The use according to claim 15, wherein sais proliferative disease is cancer, preferably wherein said cancer is selected from a cancer where COL6A3 is overexpressed, mutated, and/or a COL6A3-derived tumor-associated antigen is presented. An in vitro method for treating cancer or COL6A3-positive premalignancy, wherein said cancer is selected from a cancer where COL6A3 is overexpressed, mutated, and/or a COL6A3-derived tumor-associated antigen is presented, the method comprising: a) transforming a cell obtained from a subject in need of a cancer treatment with at least one vector according to claim 9 to produce a transformed cell; and b) expanding the transformed cell to produce a plurality of transformed cells. An in vitro method for detecting cancer in a biological sample comprising: a) contacting the biological sample with the antigen recognizing construct according to any one of claims 1 to 7; 45 b) detecting binding of the antigen recognizing construct to the biological sample, wherein said cancer is selected from a cancer where COL6A3 is overexpressed, mutated, and/or a COL6A3-derived tumor-associated antigen is presented. 19. An ex vivo method for manufacturing a COL6A3 specific antigen recognizing construct expressing host cell, comprising a. b. c. d. providing a suitable host cell, preferably a mammalian cell, more preferably a human cell, most preferred a human T lymphocyte, providing a genetic construct comprising a coding sequence encoding the antigen recognizing construct according to any of claims 1 to 7, introducing said genetic construct into said suitable host cell, and expressing said genetic construct by said suitable host cell.
NZ805217A 2018-11-05 Novel engineered t cell receptors and immune therapy using the same NZ805217A (en)

Publications (1)

Publication Number Publication Date
NZ805217A true NZ805217A (en) 2023-11-24

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