Fig. 1

a Maturation of Mesothelin (MSLN). MSLN is initially expressed on the membrane of cancer cells as a 71 kDa precursor protein which is cleaved by the endoprotease Furin to release the 31 kDa Megakaryocyte Potentiating Factor (MPF). The mature 40 kDa-MSLN remains bound to the cell membrane via a glycophosphatidylinositol (GPI) anchor. Surface MSLN can also be released from the GPI anchor by proteases, resulting in a soluble form of MSLN (soluble MSLN-related peptide - SMRP). b Anti-MSLN CAR Generations. The scFv of MSLN CAR T cells binds membrane-bound MSLN and the signaling depends on the CAR generation used. The endodomain of first generation CARs contains CD3ζ only; in second generation CARs, there is the addition of a single costimulatory domain (often CD28 or 4–1-BB); and in third generation CARs, two costimulatory domains are incorporated