The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning
Open accessAbstract
Adoptive cell therapy with tumor-targeted T cells is a promising approach to cancer therapy. Enhanced clinical outcome using this approach requires conditioning regimens with total body irradiation, lymphodepleting chemotherapy, and/or additional cytokine support. However, the need for prior conditioning precludes optimal application of this approach to a significant number of cancer patients intolerant to these regimens. Herein, we present preclinical studies demonstrating that treatment with CD19-specific, chimeric antigen receptor (CAR)–modified T cells that are further modified to constitutively secrete IL-12 are able to safely eradicate established disease in the absence of prior conditioning. We demonstrate in a novel syngeneic tumor model that tumor elimination requires both CD4+ and CD8+ T-cell subsets, autocrine IL-12 stimulation, and subsequent IFNγ secretion by the CAR+ T cells. Importantly, IL-12–secreting, tumor-targeted T cells acquire intrinsic resistance to T regulatory cell–mediated inhibition. Based on these preclinical data, we anticipate that adoptive therapy using CAR-targeted T cells modified to secrete IL-12 will obviate or reduce the need for potentially hazardous conditioning regimens to achieve optimal antitumor responses in cancer patients.
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Cites
Interleukin-12 and the regulation of innate resistance and adaptive immunity
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Self-citationA Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer
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Cited by
Chimeric Antigen Receptor Therapy
June, C. H., & Sadelain, M. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1706169 · Cited by 2,331
Self-citationAdoptive immunotherapy for cancer: harnessing the T cell response
Restifo, N. P., Dudley, M. E., & Rosenberg, S. A. (2012) · Nature Reviews Immunology · doi:10.1038/nri3191 · Cited by 1,688
The Basic Principles of Chimeric Antigen Receptor Design
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Self-citationRoles of IFN-γ in tumor progression and regression: A review
Jorgovanovic, D., Song, M., Wang, L., & Zhang, Y. (2020) · Biomarker Research · doi:10.1186/s40364-020-00228-x · Cited by 1,234
Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion
Castro, F., Cardoso, A. P., Gonçalves, R. M., Serre, K., & Oliveira, M. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00847 · Cited by 1,224
Metadata
- Authors
- Pegram, H. J., Lee, J. C., Hayman, E. G., Imperato, G. H., Tedder, T. F., Sadelain, M., & Brentjens, R. J.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-05-03
- Volume
- 119
- Issue
- 18
- Pages
- 4133-4141
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2046562334
- Cited by
- 678
- References
- 40
- FWCI
- 16.76
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Pegram, H. J., Lee, J. C., Hayman, E. G., Imperato, G. H., Tedder, T. F., Sadelain, M., & Brentjens, R. J. (2012). Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood. https://doi.org/10.1182/blood-2011-12-400044
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