Methods for proliferation of antigen-specific T cells

摘要

Methods for expansion of antigen-specific T cells are provided. Said methods include following steps: generating antigen-specific T cells by stimulation of T cells with antigen A; introducing genes encoding immune recognition molecule specific to major histocompatibility complex (MHC) molecule bound with a peptide derived from antigen B into the antigen A specific T cell to produce bi-specific T cells recognizing both target cells expressing antigen A peptide associated MHC and target cells expressing antigen B peptide associated MHC; stimulating the bi-specific T cells by antigen A for expansion of the bi-specific T cells in vitro or in vivo. Methods of the present invention can be applied to expand various of T cells with specific to cancer cells with tumor antigen peptide loaded MHC molecules for adoptive therapy against unmet medical need such as tumors etc.

主权项

1. A method for expanding bi-specific T cells, comprising:
(1) stimulating T cells with antigen A to generate T cells specific to a peptide-MHC complex of antigen A, (2) transferring a gene encoding an immune recognition molecule for targeting a peptide-MHC complex of antigen B into the T-cells specific to the peptide-MHC complex of antigen A to obtain bi-specific T-cells that are specific to both antigen A and antigen B, and (3) stimulating the bi-specific T-cells with antigen A, thereby expanding the bi-specific T-cells, wherein antigen A is a virus, bacterium, amino acid peptide, chimeric protein, or allogeneic antigen with more than 7 and less than 35 amino acids, wherein the immune recognition molecule for targeting a peptide-MHC complex of antigen B is melanoma differentiation antigen gp100-specific T cell receptor (TCR), and wherein the gene encoding melanoma differentiation antigen gp 100-specific TCR comprises SEQ ID NO: 1 encoding the TCR α subunit and SEQ ID NO:2 encoding the TCR β subunit.