By making use of various recombinant FasL proteins alone or in tandem, Fas agonist monospecific antibodies, and dual-specificity strategies, we present here extensive biochemical evidence of a highly undervalued Fas-directed tumor cytotoxicity mechanism with a great potential to enhance Ag-mediated cytotoxicity of CAR-T-based cell therapies and general immunotherapies. The gene discussed is FAS; the disease is neoplasm.