Genetic engineering of T cells with receptors from NY-ESO-1-specific tumor-recognizing CD4+ T cell as a novel approach for adoptive T cell therapy.

Background Tumor antigen-specific CD4 T cells generally orchestrate and regulate innate and adaptive immune cells to provide immune surveillance against malignancy. However, activation of antigen-specific CD4 T cells is restricted at local tumor sites where antigen-presenting cells are frequently dysfunctional, which can cause rapid exhaustion of anti-tumor immune responses. Herein, we characterize anti-tumor effects of a unique human CD4 helper T cell subset that directly recognizes the cytoplasmic tumor antigen, NY-ESO-1, presented by MHC class II (MHC-II) on cancer cells. In addition, we clone the TCR gene from tumor-recognizing CD4 T cells (TR-CD4) and test the function of TCR gene-engineered cells.