Compositions and libraries comprising recombinant t-cell receptors and methods of using recombinant t-cell receptors

Abstract

Provided are recombinant polynucleotides, including expression vectors encoding an alpha chain and / or a beta chain of a TCR having amino acid sequences from any of novel the AL, KQ, PP, 19305CD8, BB,KB, ST, JD, 19305DP, PB-P, PB-T, and PB 13.2 T Cell Receptors (TCRs) that are embodiments of the invention. Cells comprising the polynucleotides are provided, as are libraries of the recombinant polynucleotides and expression vectors. Methods are provided and involve administering to an individual modified human T cells that express a novel recombinant TCR. The methods are for prophylaxis and / or therapy of an individual diagnosed with, suspected of having or at risk for developing or recurrence of a cancer, wherein the cancer includes cancer cells which express NY-ESO-1 and / or its highly homologous LAGE-1 antigen.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims priority to US Provisional Patent Application No. 62 / 275,600, filed January 6, 2016, the disclosure of which is incorporated herein by reference. technical field [0003] The present disclosure relates generally to immunotherapy, and more particularly to recombinant T cell receptors that can confer direct tumor recognition on T cells. Background technique [0004] Tumor antigen-specific T cells recognize and kill cancer cells by employing unique T cell receptor (TCR) alpha and beta chain complexes specific for tumor antigen peptide / HLA complexes. The extremely diverse TCR alpha / beta sequences individually determine peptide specificity, HLA restriction and recognition strength. Genetic engineering of polyclonally expanded peripheral T cells with tumor antigen-specific TCRs generates large numbers of tumor antigen-specific T cells that can be used for adoptive T cell therapy in cancer patients by ...

AI Technical Summary

Problems solved by technology

Currently, only a small number of therapeutic TCR gene products have been tested in clinical trials, which significantly limits the applicability of this powerful therapeutic strategy to patients restricted by their HLA type and antigen expression in cancer cells

Accordingly, there is a continuing unmet need for improved compositions and methods for use in adoptive immunotherapy involving recombinant TCRs

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