Combination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors
Open accessAbstract
Checkpoint blockade (CPB) therapy can elicit durable clinical responses by reactivating an exhausted immune response. However, response rates remain limited, likely secondary to a lack of a tumor-reactive immune infiltrate. Chimeric antigen receptor (CAR) T cells may provide the necessary tumor-targeting immune infiltrate and a highly specific antitumor immune response. This can be further amplified by the addition of CPB agents, which serve to counteract the immune inhibitory environment undermining optimal CAR T cell efficacy. Herein, we review preclinical and clinical combination therapy with CAR T cells and CPB agents, with a focus on solid tumor malignancies.
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Key roles of TGF-β1 in suppressing the adaptive immune system are apparent from the lymphoproliferative autoimmune phenotype of Tgfb1−/− mice and similar phenotypes following selective ablation of TGF-β signaling components within CD4+ and CD8+ T cells.
“Key roles of TGF-β1 in suppressing the adaptive immune system are apparent from the lymphoproliferative autoimmune phenotype of Tgfb1−/− mice197–199, and similar phenotypes following selective ablation of TGF-β signaling components within CD4+ and CD8+ T cells200.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [197]
α-PD-1/PD-L1 enhanced CAR-T cell therapy by rescuing CAR-T cell exhaustion.
“α-PD-1/PD-L1 enhanced CAR-T cell therapy by rescuing CAR-T cell exhaustion [341–343].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [341]
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CAR-T cell therapy: current limitations and potential strategies
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Colorectal Cancer Immunotherapy: State of the Art and Future Directions
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- Authors
- Grosser, R., Cherkassky, L., Chintala, N., & Adusumilli, P. S.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Adusumilli, Prasad S.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 36
- Issue
- 5
- Pages
- 471-482
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC7171534
- OpenAlex
- W2986629061
- Cited by
- 603
- References
- 130
- Citations by year
- 2026: 77 · 2025: 129 · 2024: 88 · 2023: 81 · 2022: 104 · 2021: 82 · 2020: 42
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 CA235667, R01 CA236615\u201301, P30 CA008748)
- U.S. Department of Defense (BC132124, CA170630, LC160212, CA180889)
- Atara Biotherapeutics
- Commonwealth Foundation for Cancer Research Foundation
- Memorial Sloan-Kettering Cancer Center
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- chimeric antigen receptor T cells, immune checkpoint blockade, combination immunotherapy, solid tumors, tumor immune microenvironment, immune exhaustion, tumor-infiltrating lymphocytes, antitumor immunity
- MeSH terms
- Antineoplastic Agents, Immunological, Receptors, Chimeric Antigen, Animals, Combined Modality Therapy, Disease Models, Animal, Humans, Neoplasms, Randomized Controlled Trials as Topic, Immunotherapy, Adoptive, Treatment Outcome, Tumor Escape, Tumor Microenvironment, Costimulatory and Inhibitory T-Cell Receptors
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