A prospective for TCR-T therapy in solid tumors: Pushing the boundaries of immunotherapy

Le résumé fourni par la source

T-cell receptor-engineered T (TCR-T) cell therapy stands out as an innovative and promising approach in cancer immunotherapy, particularly for the treatment of solid tumors. This therapy differs from the well-established chimeric antigen receptor (CAR)-T therapy, which has revolutionized the treatment of hematologic malignancies. TCR-T therapy holds a unique edge in its capacity to recognize and target intracellular antigens, thereby broadening the spectrum of potential tumor-specific antigens that can be harnessed for therapeutic purposes. The recent FDA approval of afami-cel for synovial sarcoma marks a significant milestone in the journey of TCR-T therapy. This approval underscores the clinical potential of TCR-T in targeting solid tumors and opens up new avenues for therapeutic interventions. However, the broader clinical translation of TCR-T therapy is constrained by several critical barriers: the inherent requirement for HLA matching, the potent immunosuppressive tumor microenvironment, antigen heterogeneity leading to immune escape, and the risk of fatal on-target/off-tumor toxicities. In this review, we delineate the distinctive mechanistic advantages of TCR-T cells and provide a comprehensive analysis of the biological and technical hurdles encountered in solid tumor treatment. We synthesize findings from recent clinical trials and evaluate emerging optimization strategies, including TCR affinity fine-tuning and combinatorial approaches to modulate the immune landscape. Addressing these challenges is essential to provide a roadmap for enhancing the efficacy and safety of TCR-T therapies, ultimately facilitating their widespread adoption to improve survival outcomes for patients with refractory solid malignancies.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.