Alpha-fetoprotein (AFP), a specific liver cancer marker, T cells expressing AFP-CAR selectively degranulated, released cytokines, and lysed liver cancer cells that were HLA-A*02:01 /AFP while sparing cells from multiple tissue types that were negative for either expressed proteins.CAR T-cell immunotherapy targeting intracellular/secreted solid tumor antigens can elicit a potent antitumor response.