T cell modification

Abstract

This invention relates to modified T cells that inducibly express a bioactive molecule, such as IL-7, and constitutively expresses an antigen receptor, such as a T cell receptor or chimeric antigen receptor that binds to a tumour antigen. The modified T cells may comprise a nucleic acid construct that comprises a first nucleotide sequence encoding the bioactive molecule,a second nucleotide sequence encoding the antigen receptor;an inducible promoter operably linked to the first nucleotide sequence and a constitutive promoter operably linked to the second nucleotide. Nucleic acid constructs andvectors are provided, as well as T cells comprising such constructs and vectors and therapeutic methods and uses thereof.

Description

technical field [0001] The present invention relates to the modification of T cells to increase their cytotoxic activity, and the use of the modified T cells in immunotherapy, for example in the treatment of cancer. Background technique [0002] T cells (or T lymphocytes) are found to be widely distributed in tissues and tumor environments. T cells are distinguished from other lymphocytes by the presence of the T cell receptor (TCR) on the cell surface. TCRs are multisubunit transmembrane complexes that mediate antigen-specific activation of T cells. TCRs confer antigen specificity to T cells by recognizing antigenic peptide ligands presented on target cells through major histocompatibility complex (MHC) molecules. [0003] Although peptides derived from altered or mutated proteins in tumor target cells can be recognized as foreign by T cells expressing specific TCRs, many antigens on tumor cells are simply upregulated or overexpressed (so-called autoantigens), And does n...

AI Technical Summary

Problems solved by technology

Therefore, methods for the safe delivery of cytokines such as IL-7 and other bioactive molecules to T cells remain undefined

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