Authors
Huiwen Zhang, Juwei Gao, Zipeng Zhang, Bo Zhang
Published in
Immunotherapy. Volume 17. Issue 14. Pages 1039-1057. Epub Sep 15, 2025.
Abstract
With the rapid advancements in oncology, immunology, and molecular biology, immunotherapy has emerged as a cornerstone of anti-tumor treatment, complementing traditional modalities such as surgery, radiotherapy, and chemotherapy. Among the many immunotherapy strategies, adoptive cell therapy (ACT) is the most representative one. A key technology within ACT is chimeric antigen receptor (CAR) T-cell therapy, a precision-targeted treatment that leverages genetic engineering to modify T cells, enabling them to express antigen-specific receptors independent of major histocompatibility complex (MHC) restrictions. In recent years, continuous optimization of CAR-T therapy has been leading to remarkable clinical outcomes in oncology. However, its efficacy is significantly compromised by T-cell exhaustion, characterized by reduced proliferative capacity, attenuated anti-tumor activity, and limited persistence. Notably, CAR-T cell exhaustion is primarily driven by repeated tumor antigen stimulation, sustained autonomous activation of CAR constructs, and the immunosuppressive tumor microenvironment (TME), collectively contributing to disease relapse in hematologic malignancies and limited efficacy in solid tumors. Therefore, it is important to elucidate and inhibit the mechanism of CAR-T cell dysfunction to improve its efficacy. Overcoming these challenges will facilitate the development of CAR-T cells with sustained proliferative potential and tumor clearance.
PMID:
40948336
Bibliographic data and abstract were imported from PubMed on 29 Oct 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 14
- Comments 0