Mr1 restricted t cell receptors for cancer immunotherapy

Abstract

The invention relates to a method of isolating a T cell that expresses a T cell receptor capable of binding specifically to an antigen presented by a cancer cell in association with an MR molecule. The method comprises the steps of (a) providing a preparation of T cells, (b) contacting the preparation with cancer cells expressing MR1 protein; (c) isolating a T cell that is specifically reactive tosaid cancer cells. The invention further relates to a method of preparing a T cell preparation expressing select MR1 recognizing T cell receptors from transgene expression vectors, the use of such Tcell preparations in treatment of cancer, and to collections of MR1 reactive T cell receptor encoding nucleic acids and cells.

Description

[0001] The present invention relates to the identification of tumor-reactive human T-cell antigen receptors (TCRs) restricted to the non-polymorphic antigen-presenting molecule MR1. Functional TCR transcripts were isolated from clones representing a novel human T-cell population (discovered by the inventors and termed MR1T cells) that was expressed in an MR1-dependent manner without the addition of any foreign antigen. way to react with tumor cells expressing MR1. The present invention also relates to the use of MR1-restricted tumor-responsive TCR gene sequences in cancer therapy. Background technique [0002] T lymphocytes can detect a variety of different nonpeptide antigens presented by nonpolymorphic cell surface molecules, including lipids and phosphorylated isoprenoids. The diverse phenotypes and functional properties of these T cells serve specific roles in protecting the host from infection, autoimmunity, and cancer. The T cell repertoire directed against nonpeptide ...

AI Technical Summary

Problems solved by technology

Extreme polymorphism of MHC genes limits application of this method to patients expressing unique MHC alleles

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