A preparation of autologous T-lymphocytes that have been genetically modified to express a killer cell immunoglobulin-like receptor (KIR)-based chimeric antigen receptor (CAR) consisting of an anti-mesothelin (MSLN) single chain variable fragment (scFv) fused to the transmembrane and cytoplasmic domains of the stimulatory KIR 2DS2 (KIR2DS2), and the immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor protein and costimulatory chain DAP12, with potential immunomodulating and antineoplastic activities. Upon administration, the autologous anti-MSLN KIR-CAR-transduced T-cells SynKIR-110 specifically target and kill MSLN-expressing tumor cells. Mesothelin, a tumor-associated antigen (TAA) and cell surface glycoprotein involved in cell adhesion, is overexpressed in a variety of cancer cell types. KIR is normally expressed by natural killer (NK) cells, and KIR-based CAR may decrease T-cell exhaustion and enhance T-cell persistence.