Engineering chimeric antigen receptor-T cells for cancer treatment
Open accessAbstract
Intratumor heterogeneity of tumor clones and an immunosuppressive microenvironment in cancer ecosystems contribute to inherent difficulties for tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has been successfully applied in the treatment of B-cell malignancies, underscoring its great potential in antitumor therapy. However, functional challenges of CAR-T cell therapy, especially in solid tumors, remain. Here, we describe cancer-immunity phenotypes from a clonal-stromal-immune perspective and elucidate mechanisms of T-cell exhaustion that contribute to tumor immune evasion. Then we assess the functional challenges of CAR-T cell therapy, including cell trafficking and infiltration, targeted-recognition and killing of tumor cells, T-cell proliferation and persistence, immunosuppressive microenvironment and self-control regulation. Finally, we delineate tumor precision informatics and advancements in engineered CAR-T cells to counteract inherent challenges of the CAR-T cell therapy, either alone or in combination with traditional therapeutics, and highlight the therapeutic potential of this approach in future tumor precision treatment.
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Because antigen targets used for anti-CRC CAR T-cell therapy are often expressed in normal cells, accurate recognition of tumor-associated antigens (TAAs) is difficult, resulting in a therapy with low specificity.
“given that the antigen targets used for anti-CRC CAR T-cell therapy are often expressed in normal cells, the accurate recognition of tumor-associated antigens (TAAs) is rather difficult, resulting in a therapy with low specificity [140]”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [140]
Reconstructed and expanded CAR-T cells are exposed to the patient's tumor microenvironment, thereby inducing the senescent phenotype of CAR-T.
“The reconstructed and expanded CAR-T cells are exposed to the patient's tumor microenvironment, thereby inducing the senescent phenotype of CAR-T [122, 123].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [122]
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- Authors
- Ye, B., Stary, C. M., Li, X., Gao, Q., Kang, C., & Xiong, X.
- Affiliations
- Renmin Hospital of Wuhan University (CN)
- Stanford Medicine (US)
- Central South University (CN)
- Tianjin Medical University (CN)
- Corresponding author
- Kang, Chunsheng
- Xiong, Xiaoxing
- Venue
- Molecular Cancer
- Published
- 2018-02-15
- Volume
- 17
- Issue
- 1
- Pages
- 32-32
- ISSN
- 1476-4598 (ISSN-L)
- PMC
- PMC5815249
- OpenAlex
- W2797465562
- Cited by
- 95
- References
- 133
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 11 · 2023: 17 · 2022: 14 · 2021: 4 · 2020: 16 · 2019: 9 · 2018: 9 · 2017: 1
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Cancer (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- NationalNatural Science Foundation of China (81571147)
- National Natural Science Foundation of China (81600101)
- American Heart Association award (14FTF19970029)
- Fundamental Research Funds for the Central Universities (2042016kf0078)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- chimeric antigen receptor T cells, CAR T-cell therapy, solid tumors, tumor immune evasion, T cell exhaustion, tumor microenvironment, intratumoral heterogeneity, combination immunotherapy, B-cell malignancies
- MeSH terms
- Gene Editing, Receptors, Chimeric Antigen, Animals, Genetic Engineering, Humans, Neoplasms, Phenotype, T-Lymphocytes, T-Lymphocyte Subsets, Immunotherapy, Adoptive, Tumor Escape, Precision Medicine, Tumor Microenvironment
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