The treatment landscape for unresectable soft-tissue sarcomas (STS), particularly leiomyosarcoma, remains limited, prompting innovative therapeutic strategies. One promising approach involves the use of chondroitin sulfate proteoglycan 4 (CSPG4)-specific chimeric antigen receptor (CAR)-redirected cytokine-induced killer lymphocytes (CAR.CIK). In a study, patient-derived CAR.CIK were engineered using a retroviral vector to express a second-generation CSPG4-CAR with 4-1BB costimulation. This method demonstrated significant efficacy in targeting and eliminating tumor cells from various STS histotypes, indicating a potential breakthrough in the treatment of these challenging malignancies (ref: Leuci doi.org/10.1158/1078-0432.CCR-20-0357/). The study highlights the need for further clinical trials to validate the effectiveness and safety of CAR.CIK therapy in larger cohorts, which could reshape the therapeutic options available for patients with advanced STS.