by Dr. C.H. Weaver M.D. 10/2019
Mesothelin-target chimeric antigen receptor (CAR) T-cell therapy has shown early evidence of effectiveness in patients with non–small cell lung cancer (NSCLC)
About CAR T cell therapy
CAR therapies utilize T-cells (CAR T) which are a patient’s own immune cells that are re-programmed to recognize and kill cancer cells throughout the body. The process involves the removal of some T cells from a patient, and through laboratory processes these T cells are re-programmed to identify a patient’s cancer cells.
Once the T cells have been programmed to identify a patient’s cancer cells, they are replicated in the laboratory in very large numbers and infused back into the patient. The re-programmed T cells circulate throughout the body where the identify cancer cells and facilitate an immune attack against them. Simultaneously, the T cells are also replicating within the body, so that more of the immune cells can identify and attack the cancer cells.
Mesothelin is a cell-surface tumor-differentiation antigen that is frequently highly expressed in several cancers, including 65% of non-small cell lung cancer. Importantly, mesothelin is not commonly expressed on normal other lung cells which makes it an attractive therapeutic target. (2)
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Researchers are evaluating the safety and maximum tolerated dose of CAR T cells designed to attack the cell-surface protein mesothelin, which is expressed in the majority of cancer cells in mesothelioma and many individuals with NSCLC.
No significant CAR T-cell therapy-related side effects were observed and there were no cases of neurotoxicity or cytokine release syndrome which have been reported to occur with some CAR T cell treatments. Researchers specifically monitored patients for on-targeted, off-tumor side effects but found no evidence of toxicity.
Thirteen patients at the time of reporting had detectable CAR T cells in their peripheral blood from day 1 to 38 weeks after infusion. T-cell persistence appeared associated with a 50% or greater serial serum soluble mesothelin-related peptide levels and evidence of tumor regression.
- Morello A, Sadelain M, Adusumilli PS. Mesothelin-targeted CARs: driving T cells to solid tumors. Cancer Discov. 2016;6(2):133-146. doi: 10.1158/2159-8290.CD-15-0583.
- Adusumilli PS, Cherkassky L, Villena-Vargas J, et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med. 2014;6(261):261ra151. doi: 10.1126/scitranslmed.3010162.
- Adusumilli PS, Zauderer M, Rusch V, et al: A phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR-T cells. 2019 AACR Annual Meeting. Abstract CT036. Presented March 31, 2019.