T cell receptors and methods of use thereof

A cell receptor, NY-ESO-1TCR technology, applied in animal cells, genetically modified cells, using vectors to introduce foreign genetic material, etc., can solve problems that hinder the comprehensive analysis of anti-tumor T cell specificity

Pending Publication Date: 2021-12-14
UNIV HEALTH NETWORK
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the sheer number of nonmutated antigens and the high polymorphism of HLA genes may have hampered comprehensive analysis of the specificity of antitumor T cell responses to nonmutated antigens

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  • T cell receptors and methods of use thereof
  • T cell receptors and methods of use thereof
  • T cell receptors and methods of use thereof

Examples

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Embodiment 1

[0208] TILs were isolated from metastatic melanoma patients, followed by polyclonal expansion in vitro and examined for NY-ESO-1 antigen specificity for the HLA-B*07:02 allele. A combination of structure-based and functional assays using peptide / HLA (pHLA) multimers has been used to measure antigen-specific T cell responses. Using pHLA multimers with previously known NY-ESO-1 60-72 The peptides stained T cells (Figure 1). TIL shows to B*07:02 / NY-ESO-1 60-72 Multimers were positive. According to ELISPOT analysis, multimer-positive T cells secreted detectable IFN-γ in an HLA-restricted peptide-specific manner ( figure 2 ).

[0209] Multimer-positive anti-tumor T cells were collected and their TCR genes were molecularly cloned (Figure 3). Antigen specificity and functional reactivity of cloned TCRs were verified by multimeric staining and ELISPOT assay of TCR-reconstituted T cells. When reconstituted on primary T cells, B*07:02 / NY-ESO-1 60-72 TCR-transduced T cells were s...

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Abstract

The present disclosure is directed recombinant T cell receptors capable of binding an NY-ESO-1 epitope and nucleic acid molecules encoding the same. In some embodiments, the nucleic acid molecules further comprise a second nucleotide sequence, wherein the second nucleotide sequence or the polypeptide encoded by the second nucleotide sequence inhibits the expression of an endogenous TCR. Other aspects of the disclosure are directed to vectors comprising the nucleic acid molecule and cells comprising the recombinant TCR, the nucleic acid molecule, or the vector. Still other aspects of the disclosure are directed to methods of using the same. In some embodiments, the methods comprise treating a cancer in a subject in need thereof.

Description

[0001] Cross References to Related Applications [0002] This PCT application claims the benefit of priority to U.S. Provisional Application No. 62 / 813,644, filed March 4, 2019, which is hereby incorporated by reference in its entirety. [0003] References to Sequence Listings Submitted Electronically via EFS-WEB [0004] The contents of the electronically filed Sequence Listing (name: 4285_003PC01_Seqlisting_ST25.txt, size: 28,117 bytes; and date created: March 3, 2020) are hereby incorporated by reference in their entirety. technical field [0005] The present disclosure provides recombinant T cell receptors ("TCRs") that specifically bind human NY-ESO-1 and uses thereof. Background of the invention [0007] Immunotherapy has emerged as a key tool in the fight against a variety of diseases, including cancer. T cell therapy is at the forefront of the development of immunotherapeutics, and adoptive transfer of antitumor T cells has been shown to induce clinical responses i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/62A61K31/675A61K31/7076A61K35/12A61K35/17A61K38/20A61P35/00C07F9/6584C07K14/705C07K14/725C07K14/74C07K19/00C12N15/113C12N15/12C12N15/55C12N15/867C12N5/0783C12N5/10G01N33/566
CPCA61K31/675A61K31/7076A61K35/17A61K38/20A61P35/00C12N15/62G01N2333/70539G01N33/56972G01N33/505G01N33/574C07K14/7051C07K2319/03A61K31/713C07K14/71C07K14/70539C07K2319/00C07K2319/21C07K2319/33C12N2740/13043A61K2039/5156A61K2039/5158A61K39/001188C12N2510/00C12N5/0636A61K2300/00C07K16/30C12N15/1138C07K16/2809C12N2310/14C07K2317/622C07K2317/31C07K16/3076C07K2317/565C07K2319/02C07K2319/30C12N9/22C12N15/86
Inventor 平野直人村田健二佐生嘉代子
Owner UNIV HEALTH NETWORK
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