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Peer-reviewedCC BY 4.0Frontiers in Immunology

CAR-T cell therapy for solid tumors: antigen landscape, biological barriers, and engineering strategies for clinical translation

  • Qian Niu1
  • Meng Li2
  • Cheng-Yi Zhang3
  • Qian Li4
  • Meng Wang3
  • An-Dong Liu3
4 affiliations
  1. 1Department of Respiratory and Critical Care Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital
  2. 2Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  3. 3School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology
  4. 4Department of Pathology, Zhongnan Hospital of Wuhan University
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Abstract

Chimeric Antigen Receptor T (CAR-T) cell therapy has emerged as a promising therapeutic option, particularly for refractory and relapsed leukemias. However, its efficacy in treating solid tumors, including lung, ovarian, gastric, and breast cancers, remains limited by several challenges. Recent studies have highlighted CAR-T cell immunotherapy as a potential treatment for these malignancies, utilizing genetically engineered T cells that target specific tumor antigens. For successful therapy, it is crucial to identify antigens that are selectively expressed on tumor cells but not on normal tissues. In lung cancer, however, the lack of specific tumor-associated antigens, the immunosuppressive tumor microenvironment, limited CAR-T cell infiltration, and off-target effects complicate the development of effective CAR-T therapies. This review outlines the fundamental structure and generation of CAR-T cells, summarizes key tumor-associated antigens targeted in clinical trials for these cancers, and discusses the current challenges and emerging strategies. The goal is to provide insights and potential approaches to enhance the design and execution of preclinical and clinical CAR-T cell therapies for these solid tumors.

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Cite

BibTeXRIS
BibTeX
@article{niu2026cart,
  title = {{CAR-T cell therapy for solid tumors: antigen landscape, biological barriers, and engineering strategies for clinical translation}},
  author = {Qian Niu and Meng Li and Cheng-Yi Zhang and Qian Li and Meng Wang and An-Dong Liu},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1968080},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1968080/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - CAR-T cell therapy for solid tumors: antigen landscape, biological barriers, and engineering strategies for clinical translation
AU  - Qian Niu
AU  - Meng Li
AU  - Cheng-Yi Zhang
AU  - Qian Li
AU  - Meng Wang
AU  - An-Dong Liu
PY  - 2026
DA  - 2026/10/09
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1968080
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1968080/full
AB  - Chimeric Antigen Receptor T (CAR-T) cell therapy has emerged as a promising therapeutic option, particularly for refractory and relapsed leukemias. However, its efficacy in treating solid tumors, including lung, ovarian, gastric, and breast cancers, remains limited by several challenges. Recent studies have highlighted CAR-T cell immunotherapy as a potential treatment for these malignancies, utilizing genetically engineered T cells that target specific tumor antigens. For successful therapy, it is crucial to identify antigens that are selectively expressed on tumor cells but not on normal tissues. In lung cancer, however, the lack of specific tumor-associated antigens, the immunosuppressive tumor microenvironment, limited CAR-T cell infiltration, and off-target effects complicate the development of effective CAR-T therapies. This review outlines the fundamental structure and generation of CAR-T cells, summarizes key tumor-associated antigens targeted in clinical trials for these cancers, and discusses the current challenges and emerging strategies. The goal is to provide insights and potential approaches to enhance the design and execution of preclinical and clinical CAR-T cell therapies for these solid tumors.
SN  - 1664-3224
ER  -