Overcoming barriers of car T-cell therapy in patients with mesothelin-expressing cancers.

One obstacle to the application of immunotherapy to solid malignancies is to overcome the existing tolerance to self-antigens. Vaccine strategies aimed at harnessing endogenous antitumor T cells are limited by the T-cell receptor repertoire, which can be detected within the thymus as central tolerance or rendered nonfunctional by post-thymic mechanisms of peripheral tolerance. Adoptive immunotherapy can overcome these obstacles, since therapeutically effective T cells can be engineered to recognize tumors. Continued advancements in novel treatments, including immunotherapy, in solid malignancies are imperative. While mesothelin is an attractive target for cancer immunotherapy given its normal expression is limited to mesothelial cells, the breakthrough for chimeric antigen receptor T-cell treatment against this antigen is still forthcoming.