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

Shiyu Wang; Tianshu Zhang; Qian Xiao

doi:10.59717/j.xinn-med.2026.100212

The Innovation Medicine > 2026 Vol. 4 > No. 2 > 100212

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

1.
Institute of Modern Biology, Nanjing University, Nanjing 210008, China
2.
The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210008, China
3.
The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing 210008, China
4.
These authors contributed equally

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Corresponding author: qian.xiao@nju.edu.cn
Received Date: December 16, 2025

Accepted Date: April 13, 2026

Published Online: April 14, 2026

The Innovation Medicine 4(2), https://doi.org/10.59717/j.xinn-med.2026.100212 | Cite this article

GRAPHICAL ABSTRACT

GRAPHICAL ABSTRACT

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. TCR-T (T-cell receptor-engineered T) therapy targets hidden internal cancer proteins as a breakthrough.
  
  The recent FDA approval of afami-cel marks a major milestone for advancing this personalized immunotherapy.
  
  Researchers leverage AI (Artificial Intelligence) and gene editing to overcome complex biological hurdles.
  
  New strategies aim to improve T-cell fitness and persistence within the suppressive tumor microenvironment.
  
  Combining TCR-T with other drugs could revolutionize care for patients with resistant solid malignancies.

ABSTRACT

ABSTRACT

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.

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Wang S., Zhang T. and Xiao Q. (2026). A prospective for TCR-T therapy in solid tumors: Pushing the boundaries of immunotherapy. The Innovation Medicine 4:100212. https://doi.org/10.59717/j.xinn-med.2026.100212

Wang S., Zhang T. and Xiao Q. (2026). A prospective for TCR-T therapy in solid tumors: Pushing the boundaries of immunotherapy. The Innovation Medicine 4:100212. https://doi.org/10.59717/j.xinn-med.2026.100212

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

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