Mesothelin-targeted chimeric antigen receptor (CAR) T-cell therapy has shown early evidence of efficacy in a phase I trial of patients with malignant pleural disease and mesothelioma, non–small cell lung cancer, or breast cancer (NCT02414269). Additionally, significant responses were seen in patients who went on to receive subsequent PD-1 checkpoint inhibition treatment. Preliminary results from the ongoing study were presented at the 2018 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting.
“We provide the first clinical evidence that combination immunotherapy with CAR T cells followed by anti–PD-1 agents can elicit responses in patients with hard-to-treat, therapy-refractory solid tumors,” said principal investigator Prasad S. Adusumilli, MD, when presenting the current findings at the ASGCT meeting.
Mesothelin is a cell-surface tumor-differentiation antigen that is frequently highly expressed in several cancers, including mesothelioma, lung, pancreas, breast, and ovarian. The mesothelin protein has been found to be expressed in 85% to 90% of mesotheliomas, 80% to 85% of pancreatic cancers, and 60% to 65% of lung cancers, ovarian cancers, and cholangiocarcinomas.2 On the other hand, mesothelin is not commonly expressed on normal mesothelial cells, making it an attractive therapeutic target.
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