Toxicity and management in CAR T-cell therapy
By Challice L. Bonifant, H. J. Jackson, R. Brentjens, K. Curran. Molecular Therapy: Oncolytics, 2016
839 citations recorded by the source corpus.
T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). Most notably, CAR T cells have demonstrated clinical efficacy in hematologic malignancies with more modest responses when targeting solid tumors. However, CAR T cells also have the capacity to elicit expected and unexpected toxicities including: cytokine release syndrome, neurologic toxicity, “on target/off tumor” recognition, and anaphylaxis. Theoretical toxicities including clonal expansion secondary to insertional oncogenesis, graft versus host disease, and off-target antigen recognition have not been clinically evident. Abrogating toxicity has become a critical step in the successful application of this emerging technology. To this end, we review the reported and theoretical toxicities of CAR T cells and their management.
Subfields: Genetics, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/4cd3d9e17f4511c26032eb835a5b50ac069d115c
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Citations in the corpus
- Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent anti-tumor activity (2017, neutral): “(17) Finally, CAR-engineered NK cells may also exert potentially serious toxicity, such as cytokine release syndrome (CRS) or off-tumor/on-target toxicity, as reported with CAR Tcells.(18)”
- Mesothelin-targeted CAR-T cell therapy for solid tumors (2020, background): “often occur in gastrointestinal, pulmonary, and hematological tissues and can highly vary in severity from manageable manifestations to severe toxicity and death [100].”
- Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses (2018, neutral): “However, CARs made with high-affinity scFvs have limited capacity in discriminating antigen density, which has led to dangerous reactivity against healthy organs expressing a low level of antigens (Bonifant et al., 2016; Morgan et al., 2010).”
- Cytokine release syndrome (2018, background): “Subsequent studies confirmed that administration of monoclonal antibodies against IL-6 (siltuximab) and its receptor (tocilizumab) led to rapid resolution of CRS symptoms [29, 31, 33, 71].”