We compared the potential therapeutic effect of M1xx, a MSLN-directed CAR T cell containing a CD28 costimulatory domain and a CD3ζ chain with mutations in the two distal ITAMs, with two conventional second-generation MSLN-CAR T cells containing either CD28 (M28z) or 4-1BB (MBBz) costimulatory domain.20 Functionality and therapeutic efficacy of M1xx CAR T cells was assessed in vitro and in two in vivo orthotopic preclinical models of ovarian cancer. Here, CD28 is linked to ovarian cancer.