Significantly increased anti-tumor activity of carcinoembryonic antigen-specific chimeric antigen receptor T cells in combination with recombinant human IL-12
Open accessAbstract
BACKGROUND AIMS: Chimeric antigen receptor T cells (CAR-T cells) have been successfully used in treatments of hematological tumors, however, their anti-tumor activity in solid tumor treatments was limited. As IL-12 increases T-cell immune functions, we designed carcinoembryonic antigen (CEA) specific CAR-T (CEA-CAR-T) cells and, for the first time, used them in combination with recombinant human IL-12 (rhIL-12) to treat several types of solid tumors. METHODS: In vitro anti-tumor activity of CEA-CAR-T cells in combination with rhIL-12 was confirmed by evaluation of CEA-CAR-T cell activation, proliferation, and cytotoxicity after co-incubation with CEA-positive or CEA-negative human tumor cells. In vivo anti-tumor activity of CEA-CAR-T cells in combination with rhIL-12 was confirmed in a xenograft model in nude mice for treatments of several types of solid tumors. RESULTS: In vitro experiments confirmed that rhIL-12 significantly increased the activation, proliferation, and cytotoxicity of CEA-CAR-T cells. Similarly, in vivo experiments found that CEA-CAR-T cells in combination with rhIL-12 had significantly enhanced anti-tumor activity than CEA-CAR-T cells in growth inhibition of newly colonized colorectal cancer cell HT-29, pancreatic cancer cell AsPC-1, and gastric cancer cell MGC803. CONCLUSIONS: These works confirmed that simultaneous use of cytokines, for example, rhIL-12, can increase the anti-tumor activity of CAR-T cells, especially for treatments of several types of solid tumors.
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Several antigens being evaluated as candidates for anti-CRC CAR-T cell therapy have shown efficacy in CRC preclinical models, including carcinoembryonic antigen and guanylyl cyclase 2C.
“Several antigens being evaluated as candidates for anti-CRC CAR-T cell therapy have shown efficacy in CRC preclinical models, including carcinoembryonic antigen and guanylyl cyclase 2C [227,228].”
From Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer (2025) · cites this paper as [228]
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Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer
Haynes, J., & Manogaran, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26051988 · Cited by 82 · see citing works
“Several antigens being evaluated as candidates for anti-CRC CAR-T cell therapy have shown efficacy in CRC preclinical models, including carcinoembryonic antigen and guanylyl cyclase 2C [227,228].”
Recruiting Immunity for the Fight against Colorectal Cancer: Current Status and Challenges
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- Authors
- Chi, X., Yang, P., Zhang, E., Gu, J., Xu, H., Li, M., Gao, X., Li, X., Zhang, Y., Xu, H., & Hu, J.
- Affiliations
- China Pharmaceutical University (CN)
- Corresponding author
- Xu, Hanmei
- Hu, Jialiang
- Venue
- Cancer Medicine
- Publisher
- Wiley
- Published
- 2019-06-25
- Volume
- 8
- Issue
- 10
- Pages
- 4753-4765
- ISSN
- 2045-7634 (ISSN-L)
- PMC
- PMC6712469
- OpenAlex
- W2954358786
- Cited by
- 75
- References
- 38
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 12 · 2023: 13 · 2022: 11 · 2021: 11 · 2020: 8
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Science Foundation of Jiangsu Province (BK20160757)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Keywords
- chimeric antigen receptor T cells, carcinoembryonic antigen, solid tumors, T cell activation, T cell proliferation, T cell cytotoxicity, colorectal cancer, pancreatic cancer, gastric cancer, xenograft models
- MeSH terms
- Receptors, Chimeric Antigen, Animals, Carcinoembryonic Antigen, Female, Humans, Mice, Nude, Neoplasms, Recombinant Proteins, Immunotherapy, Adoptive, Apoptosis, Interleukin-12, HT29 Cells, Xenograft Model Antitumor Assays, Cell Line, Tumor, Cell Proliferation, Mice
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