The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment
Open accessAbstract
Chimeric antigen receptor (CAR) T cell therapy has shown limited efficacy for the management of solid tumor malignancies. In ovarian cancer, this is in part due to an immunosuppressive cytokine and cellular tumor microenvironment which suppresses adoptively transferred T cells. We engineered an armored CAR T cell capable of constitutive secretion of IL-12, and delineate the mechanisms via which these CAR T cells overcome a hostile tumor microenvironment. In this report, we demonstrate enhanced proliferation, decreased apoptosis and increased cytotoxicity in the presence of immunosuppressive ascites. In vivo, we show enhanced expansion and CAR T cell antitumor efficacy, culminating in improvement in survival in a syngeneic model of ovarian peritoneal carcinomatosis. Armored CAR T cells mediated depletion of tumor associated macrophages and resisted endogenous PD-L1-induced inhibition. These findings highlight the role of the inhibitory microenvironment and how CAR T cells can be further engineered to maintain efficacy.
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Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9
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Self-citationA Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer
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IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer
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Cited by
A guide to cancer immunotherapy: from T cell basic science to clinical practice
Waldman, A. D., Fritz, J. M., & Lenardo, M. J. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0306-5 · Cited by 4,154
Mechanisms of resistance to CAR T cell therapy
Shah, N. N., & Fry, T. J. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0184-6 · Cited by 959
Recent advances and discoveries in the mechanisms and functions of CAR T cells
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Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo
Rafiq, S., Yeku, O. O., Jackson, H. J., Purdon, T. J., van Leeuwen, D. G., Drakes, D. J., Song, M., Miele, M. M., Li, Z., Wang, P., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4195 · Cited by 833
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Metadata
- Authors
- Yeku, O. O., Purdon, T. J., Koneru, M., Spriggs, D., & Brentjens, R. J.
- Venue
- Scientific Reports
- Published
- 2017-09-05
- Volume
- 7
- Issue
- 1
- Pages
- 10541-10541
- ISSN
- 2045-2322 (ISSN-L)
- OpenAlex
- W2750694869
- Cited by
- 409
- References
- 54
- FWCI
- 13.68
- Type
- journal article
- Language
- en
- Open access
- gold
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