New Strategies in Engineering T-Cell Receptor Gene-Modified T Cells to More Effectively Target Malignancies

摘要

The immune system, and T cells in particular, have the ability to target and destroy malignant cells. However, anti-tumor immune responses induced from the endogenous T cell repertoire are often insufficient for the eradication of established tumors, as illustrated by the failure of cancer vaccination strategies or checkpoint blockade for most tumors. Genetic modification of T cells to express a defined T cell receptor (TCR) can provide the means to rapidly generate large numbers of tumor-reactive T cells capable of targeting tumor cells in vivo. However, cell-intrinsic factors as well as immunosuppressive factors in the tumor microenvironment can limit the function of such gene-modified T cells. New strategies currently being developed are refining and enhancing this approach, resulting in cellular therapies that more effectively target tumors and that are less susceptible to tumor immune-evasion.