Methods for Generating Antigen-Specific Effector T Cells

Simple SummaryContent extracted from patent full text and abstract with AI.

This invention describes methods and compositions for generating antigen-specific effector T cells by transiently transfecting them with RNA, particularly RNA encoding T cell receptors (TCRs) and/or FoxP3. The process uses electroporation to introduce the RNA into purified T cells, enabling these cells to specifically recognize and attack target cells (such as tumor cells, pathogen-infected cells, or cells causing autoimmunity or transplant rejection) without permanent genetic modification. This approach allows rapid, safe, and reversible programming of T cells for use in various forms of immunotherapy.

Use CasesContent extracted from patent full text and abstract with AI.

• Immunotherapy of cancers (e.g. melanoma, renal cell carcinoma, lung, breast, prostate, ovarian, or colon cancer) using patient- or donor-derived T cells programmed to recognize tumor antigens.
• Treatment of viral infections, such as HIV or hepatitis C, by generating T cells specific to virus-infected cells.
• Prevention or treatment of transplant rejection and graft-versus-host disease (GVHD) by generating regulatory T cells specific for self- or transplant-antigens.
• Treatment of autoimmune diseases with regulatory T cells (Treg) specifically programmed to target self-antigens.
• Research applications for studying antigen-specific immune responses by transiently programming T cells to specificities of interest.
• Screening and validation of candidate TCRs for clinical or experimental purposes, given the method’s reversible and non-permanent nature.

BenefitsContent extracted from patent full text and abstract with AI.

• Avoids permanent genetic modification, reducing risks of insertional mutagenesis and oncogenesis associated with viral transduction.
• Rapid and high-efficiency generation of functional antigen-specific T cells using RNA electroporation.
• Applicable to both CD4+ and CD8+ T cells, and can generate a variety of effector or regulatory cell types (including Treg via FoxP3 transfection).
• Transfected T cells maintain effector function after cryopreservation, enabling manufacturing of therapy doses in advance and batch processing.
• Safety is enhanced due to transient expression of the introduced proteins; effects are reversible and non-heritable.
• Technique can be performed on unstimulated ('resting') T cells, simplifying preparation and broadening applicability.
• Facilitates faster and safer screening of TCR candidates for therapeutic development.
• Versatile: applicable to a wide spectrum of antigens (tumor, pathogen, self, transplant) and a wide range of diseases.

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

The invention relates to T cells transiently transfected with RNA, especially RNA encoding a T cell receptor and/or FoxP3, and to 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.