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CAR-T cell therapy: current limitations and potential strategies
Open accessAbstract
Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical responses with certain subsets of B cell leukemia or lymphoma, many challenges limit the therapeutic efficacy of CAR-T cells in solid tumors and hematological malignancies. Barriers to effective CAR-T cell therapy include severe life-threatening toxicities, modest anti-tumor activity, antigen escape, restricted trafficking, and limited tumor infiltration. In addition, the host and tumor microenvironment interactions with CAR-T cells critically alter CAR-T cell function. Furthermore, a complex workforce is required to develop and implement these treatments. In order to overcome these significant challenges, innovative strategies and approaches to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. In this review, we discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CAR-T cell therapy in both hematological malignancy and solid tumors.
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“Despite their general tolerability, immune checkpoint inhibitors (ICIs) may induce cytokine storms in patients, and T cell-engaging bispecific antibodies and TCR/CAR-T engineered T cells, contingent on the target, could result in significant off-target tissue destruction, leading to associated morbidity and mortality (Sterner and Sterner, 2021; Johnson et al., 2022).”
From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Sterner and Sterner, 2021
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“To address this, various immunotherapeutic strategies have emerged, including adoptive cell transfer, primarily utilizing genetically modified T cells expressing chimeric antigen receptors (CAR T-cells) to recognize and eliminate cancer cells directly (Sterner and Sterner, 2021). Adjuvant therapies, such as dendritic cell, mRNA, and peptide-based vaccinations, aim to boost the patient’s anticancer”
From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Sterner and Sterner, 2021
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“Despite their general tolerability, immune checkpoint inhibitors (ICIs) may induce cytokine storms in patients, and T cell-engaging bispecific antibodies and TCR/CAR-T engineered T cells, contingent on the target, could result in significant off-target tissue destruction, leading to associated morbidity and mortality (Sterner and Sterner, 2021; Johnson et al., 2022).”
From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Sterner and Sterner, 2021
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Metadata
- Authors
- Sterner, R. C., & Sterner, R. M.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Sterner, Rosalie M.
- Venue
- Blood Cancer Journal
- Published
- 2021-04-06
- Volume
- 11
- Issue
- 4
- Pages
- 69-69
- ISSN
- 2044-5385 (ISSN-L)
- PMC
- PMC8024391
- OpenAlex
- W3148729173
- Cited by
- 2,926
- References
- 110
- Citations by year
- 2026: 530 · 2025: 806 · 2024: 726 · 2023: 532 · 2022: 287 · 2021: 42
- FWCI
- 48.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Blood Cancer Journal (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Wisconsin-Madison (T32-GM008692)
- Regenerative Medicine Minnesota (RMM 012819 EPC 003)
- National Institute of General Medical Sciences (T32GM008692)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- CAR T-cell therapy, chimeric antigen receptor, solid tumors, hematologic malignancies, CAR-T cell engineering, tumor microenvironment, antigen escape, CAR-T toxicity, tumor infiltration
- MeSH terms
- Receptors, Chimeric Antigen, Animals, Humans, Neoplasms, T-Lymphocytes, Immunotherapy, Adoptive, Hematologic Neoplasms, Tumor Microenvironment
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