Methods for generating antigen-specific effector T cells

Abstract

The invention relates to T cells transiently transfected with RNA, especially RNA encoding a T cell receptor and / or FoxP3, and methods of transfecting T cells with RNA by electroporation. Compositions of the invention include an effector T cell transiently transfected with RNA encoding a T cell receptor (TCR) specific for an antigen, wherein the T cell demonstrates effector function specific for cells presenting the antigen in complex with an MHC molecule. Treg cells comprising an exogenous RNA encoding FoxP3 are also provided. The transfected T cells are useful for immunotherapy, particularly in the treatment of tumors, pathogen infection, autoimmune disease, transplant rejection and graft versus host disease.

Description

technical field [0001] The present invention relates to T cells transiently transfected with RNA - in particular RNA encoding T cell receptors and / or FoxP3 - and methods of transfecting T cells with RNA by electroporation. The transfected T cells can be used for immunotherapy, especially for the treatment of tumors, pathogenic infections, autoimmune diseases, transplantation rejection and graft-versus-host disease. Background technique [0002] Cytotoxic T lymphocytes (CTLs) play a major role in tumor control and thus have great importance in the cellular regimen of cancer immunotherapy [19]. Earlier attempts at the adoptive transfer of tumor-infiltrating lymphocytes (TILs) were unsatisfactory because the transferred cells were often nonspecific and did not persist for extended periods of time, most likely due to the possible anergy phenotype of such TILs (anergic phenotype) or unable to self-guid to the tumor site [10,11]. Adoptive transfer of in vitro expanded autologous...

AI Technical Summary

Problems solved by technology

[0004] Thus, there exists a long-felt unmet need for the efficient transfer of antigen-specific TCR function to T cells that does not require retroviral vectors or other forms of transfection that may result in genomic alterations of the subject

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