Cellular therapies in sarcoma and other solid tumors.

Abstract

Purpose of review: While adoptive cell therapies such as chimeric antigen receptor T (CAR-T) cell have demonstrated efficacy in hematological malignancies, their success in solid tumors remains challenging due to tumor heterogeneity, antigen specificity, and the suppressive tumor microenvironment. This review aims to provide an overview of recent advancements in cellular therapies, in sarcomas and other solid malignancies.

Recent findings: In the field of sarcomas, the approval of afamitresgene autoleucel (afami-cel) for synovial sarcoma in Atoxiciugust 2024 marks a milestone in T cell therapy, demonstrating an objective response rate (ORR) of 39% and a median overall survival (OS) of 16.9 months in the SPEARHEAD-1 phase 2 trial. Other trials exploring NY-ESO-1 specific T-cell receptor-engineered T (TCR-T) therapies in myxoid round-cell liposarcoma (MRCL) have shown promising response rates. Beyond sarcomas, CAR-T therapies targeting CLDN18.2 in gastrointestinal cancers, GD2 in gliomas, and PSCA in prostate cancer have demonstrated varying degrees of efficacy, with ongoing research to date.

Summary: Clinically, these therapies highlight the need for improved patient selection criteria, and optimized antigen targeting. Toxicity management must also be taken into account, as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) can be severe. Further studies should focus on improving safety and T cell persistence, and refining manufacturing processes to increase accessibility and scalability.