Chimeric antigen receptor T (CAR T) cell therapy has had great success in treating B cell leukemia and lymphoma, however, remains ineffective in treating solid tumors and other hematological malignancies.1,3 Barriers to the therapeutic efficacy of CAR T cell therapy are potential life-threatening toxicity, limited CAR T cell trafficking and tumor infiltration, antigen escape, and the immunosuppressive tumor microenvironment.1 To overcome the limitations of the current CAR T cell therapies we are evaluating mucosal associated invariant T cells (MAITs) as an alternative platform to improve cancer immunotherapies targeting solid tumors. MAITs are innate-like αβ T cells with a very limited TCR repertoire that is only specific for microbial peptides derived from riboflavin and are not responsive to allogeneic peptides.6 Thus, MAITs do not mediate alloreactivity warranting their potential use as an allogeneic, off-the-shelf, CAR product, overcoming the limitation of current CAR T cell therapies as autologous products.2,4 They have a distinct cytokine profile and express various cytotoxic receptors capable of recognizing tumor cells in a CAR-independent manner, reducing the risk of toxicity and antigen escape, respectively. Moreover, they are more likely to infiltrate solid tumors in the liver and lung due to their natural homing to these tissues.4 Recently, MAITs have been enriched and expanded 200-fold from PBMCs, transduced with the CD19 CAR, and demonstrated to kill leukemia cells in a CAR-dependent manner in vitro.4,5 However, trafficking and tumor infiltration, safety, and overall anti-tumor efficacy of CAR MAITs targeting solid tumors in vivo is unknown. In this study, we demonstrate that MAITs expressing a CAR specific for mesothelin (M5 CAR) can kill a mesothelin expressing pancreatic tumor cell line, AsPC-1, in vitro with similar kinetics as conventional M5 CAR T cells. However, M5 CAR MAITs demonstrate limited anti-tumor efficacy in an in vivo AsPC-1 mice model.