A next-generation chimeric antigen receptor (CAR) cell therapy platform, termed CARMA, could shrink adoptive cell therapy manufacturing timelines from weeks to a single day, researchers reported at the 34th Annual Meeting & Preconference Programs of the Society for Immunotherapy of Cancer, or SITC 2019. The results were from a preclinical study evaluating the CARMA platform for the manufacture of an anti-mesothelin CAR cell therapy for solid tumors, including peritoneal mesothelioma, fallopian tube adenocarcinoma, adenocarcinoma of the ovary, and primary peritoneal carcinoma.

Developed by MaxCyte, Inc, in Gaithersburg, Maryland, the
CARMA platform uses peripheral blood mononuclear cells (PBMCs) from apheresis
product and modifies these immune cells with human messenger RNA (mRNA) in
transient flow electroporation (FEP) to target mesothelin. The final result is a
cryopreserved drug product.

The anti-mesothelin CAR cell therapy evaluated in the study is
known as MCY-M11 and is engineered to target mesothelin-expressing solid tumors.
The study researchers surveyed 20 development and engineering runs on the CARMA
platform.

They found that most of the cells (92%) remained viable after
flow electroporation, and the experiments showed that an average of 73% of T
cells (range, 42%-83%) and 59% of natural killer (NK) cells (range, 28%-75%) in
the MCY-M11 product expressed the mesothelin CAR.

Also, in vitro experiments with mesothelin-expressing human
tumor cell lines showed that MCY-M11 had antitumor bioactivity and target
specificity. In addition, a human mesothelin-expressing ovarian syngeneic mouse
tumor model showed that MCY-M11 had antitumor activity.

A first-in-human phase 1 study is under way to evaluate MCY-M11 in patients with advanced epithelial ovarian cancer or peritoneal mesothelioma (ClinicalTrials.gov Identifier: NCT03608618). The study is being sponsored by MaxCyte, Inc.

Reference

Kuo M, Keefe R, Li L, et al. Single-day CAR manufacturing platform using mRNA and flow electroporation technology. Poster presented at: the 34th Annual Meeting & Preconference Programs (SITC 2019); November 6–10, 2019: National Harbor, Maryland. Abstract P190.



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