MaxCyte plans to evaluate its first autologous CAR drug candidate in mesothelin-expressing solid tumors. This product candidate, MCY-M11, employs repeat infusions of mesothelin-specific human mRNA CAR-transfected into PBMCs (peripheral blood mononuclear cells) to permit “controlled persistence.” Early non-clinical testing has provided preliminary evidence of the anti-tumor activity of this drug.

MaxCyte and its collaborators at the Johns Hopkins Kimmel Cancer Center explored the various attributes of MCY-M11 in nonclinical studies. These studies found that cryopreserved MCY-M11 expressed CAR in >95% of cells, and recognized and lysed tumor cells in an antigen-specific manner. In addition, expression of CAR was detectable with retained functional activity for 5 to 7 days in vitro, with a progressive decline of CAR expression related to in vitro cell expansion.

In a murine ovarian cancer model, a single intra-peritoneal (IP) injection of MCY-M11 resulted in the dose-dependent inhibition of tumor growth and prolonged the overall survival (OS) of the mice in the study. Weekly IP (intra-peritoneal) injections of the optimized MCY-M11 dose boosted disease control and further prolonged OS, both of which improved with an increasing number of injections. No significant off-tumor toxicities were observed.

2017 AACR Annual Meeting Abstract: Development of anti-human mesothelin chimeric antigen receptor (CAR) messenger RNA (mRNA) transfected peripheral blood mononuclear cells (CARMA) for the treatment of mesothelin-expressing cancers

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