Adoptive T-Cell Therapy in Sarcomas

Abstract

Purpose of review: To summarise and evaluate the latest adoptive T-cell therapies in sarcomas, focusing on therapeutic targets, efficacy, safety, and limitations.

Recent findings: An increasing number of clinical trials are investigating adoptive T-cell therapies in sarcomas, most targeting NY-ESO-1 and MAGE-A4 through engineered T-cell receptors (TCR-T). The FDA approval of afamitresgene autoleucel for advanced synovial sarcoma and the breakthrough designation of letetresgene autoleucel for myxoid/round cell liposarcoma signify a major turning point. Chimeric antigen receptor T strategies target mainly B7H3, GD2, FGFR4, and HER2, with innovations including dual antigen targeting and safety switches. Tumour infiltrating lymphocyte therapy, including lifileucel, is under investigation with checkpoint inhibitors or oncolytic agents to enhance efficacy and manage toxicity. Adoptive T-cell therapy demonstrates early promise in sarcomas, particularly TCR-T therapy. Challenges include HLA restriction, tumour heterogeneity, and manufacturing complexity. Future strategies involving novel antigens, multi-targeting, and combinatorial regimens could broaden patient eligibility and improve therapeutic outcomes.

Keywords: Adoptive T-cell Therapy; Cancer-testis Antigen; Chimeric Antigen Receptor T; Engineered T-cell Receptor; NY-ESO-1; Sarcoma Immunotherapy; Tumour Infiltrating Lymphocyte.