CELL INTELLIGENCE · 肿瘤细胞治疗研究

Background/Objectives : Melanoma antigen recognized by T cells 1 (MART-1) is a tumor-associated antigen overexpressed in melanoma cells that serves as a target for different immunotherapeutic strategies. These approaches differ substantially in their efficacy and safety and are associated with various immunologic challenges, including the incidence of autoimmunity. Although multiple clinical trials evaluated anti-MART-1 immunotherapies, the available evidence is highly heterogeneous and requires systematic evaluation. The present study aimed to systematically summarize and descriptively compare the reported efficacy and safety of different MART-1-targeted immunotherapeutic strategies. Methods : Clinical trial registries and bibliographic databases were systematically searched to identify clinical trials investigating anti-MART-1 immunotherapies. Data on the objective response rate (ORR), median relapse-free survival (RFS), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and adverse effects were extracted and structured. Potential immunologic challenges underlying the observed outcomes were also discussed. Results : Fifty-four clinical trials comprising 1292 treated patients were included, of whom 517 entered their trial with measurable disease and were evaluable for an objective response by RECIST. Higher objective response rates were reported in the autologous cell transfer and TCR-T trials than in the peptide- and DNA-based vaccine trials, whereas the vaccine trials reported fewer immune-related adverse events. These are uncontrolled cross-trial observations. The cell-based regimens were administered after non-myeloablative lymphodepletion and usually with high-dose IL-2, whereas the vaccination protocols were not, so the differences between modalities cannot be attributed to MART-1 targeting alone. No meta-analysis and no formal comparative efficacy analysis were performed. Conclusions : Based on the available data, MART-1-targeted immunotherapeutic strategies showed distinct efficacy and safety profiles. Higher objective response rates were reported in some adoptive cell therapy trials, together with a higher frequency of immune-related adverse events; these are uncontrolled cross-trial observations, and the contribution of concomitant lymphodepletion and IL-2 cannot be separated from that of MART-1 targeting. Peptide- and DNA-based vaccine approaches were associated with fewer immune-related adverse events and may warrant further evaluation as components of combined regimens.