CAR-T Therapy of Mesothelin Expressing Cancers

Division Of Basic Sciences - Nci

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Abstract

We have identified the major protease sites in mesothelin and prepared a monoclonal antibody, 15B6, that binds next to cell membrane at the protease sensitive region and inhibits MSLN shedding. 15B6 reacts with the 2 mesothelin isoforms containing a M or V at position 593. Mab 15B6 makes very active CAR-T cells whose activity is not blocked by shed mesothelin. The 15B6 CAR-T cells have greatly superior anti-tumor activity in mice than CAR-T cells targeting an epitope in shed mesothelin. The sequences in the mab 15B6 have been humanized.