The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
IL-10-expressing CAR T cells resist dysfunction and mediate durable clearance of solid tumors and metastases
Open accessAbstract
The success of chimeric antigen receptor (CAR) T cell therapy in treating several hematopoietic malignancies has been difficult to replicate in solid tumors, in part because of T cell exhaustion and eventually dysfunction. To counter T cell dysfunction in the tumor microenvironment, we metabolically armored CAR T cells by engineering them to secrete interleukin-10 (IL-10). We show that IL-10 CAR T cells preserve intact mitochondrial structure and function in the tumor microenvironment and increase oxidative phosphorylation in a mitochondrial pyruvate carrier-dependent manner. IL-10 secretion promoted proliferation and effector function of CAR T cells, leading to complete regression of established solid tumors and metastatic cancers across several cancer types in syngeneic and xenograft mouse models, including colon cancer, breast cancer, melanoma and pancreatic cancer. IL-10 CAR T cells also induced stem cell-like memory responses in lymphoid organs that imparted durable protection against tumor rechallenge. Our results establish a generalizable approach to counter CAR T cell dysfunction through metabolic armoring, leading to solid tumor eradication and long-lasting immune protection. CAR T cells engineered to express IL-10 eradicate solid tumors and metastases.
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Cited by
CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors
Peng, L., Sferruzza, G., Yang, L., Zhou, L., & Chen, S. (2024) · Cellular & Molecular Immunology · doi:10.1038/s41423-024-01207-0 · Cited by 373
Metadata
- Authors
- Zhao, Y., Chen, J., Andreatta, M., Feng, B., Xie, Y.-Q., Wenes, M., Wang, Y., Gao, M., Hu, X., Romero, P., Carmona, S., Sun, J., Guo, Y., & Tang, L.
- Venue
- Nature Biotechnology
- Published
- 2024-01-02
- Volume
- 42
- Issue
- 11
- Pages
- 1693-1704
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W4390507337
- Cited by
- 299
- References
- 47
- FWCI
- 45.73
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhao, Y., Chen, J., Andreatta, M., Feng, B., Xie, Y.-Q., Wenes, M., Wang, Y., Gao, M., Hu, X., Romero, P., Carmona, S., Sun, J., Guo, Y., & Tang, L. (2024). IL-10-expressing CAR T cells resist dysfunction and mediate durable clearance of solid tumors and metastases. Nature Biotechnology. https://doi.org/10.1038/s41587-023-02060-8
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