CART Cell Toxicities: New Insight into Mechanisms and Management
T cells genetically engineered with chimeric antigen receptors (CART) have become a potent class of cancer immunotherapeutics. Numerous clinical trials of CART cells have revealed remarkable remission rates in patients with relapsed or refractory hematologic malignancies. Despite recent clinical suc...
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| Format: | Article |
| Language: | English |
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SAABRON PRESS
2020-11-01
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| Series: | Clinical Hematology International |
| Subjects: | |
| Online Access: | https://www.atlantis-press.com/article/125946348/view |
| _version_ | 1797230746171080704 |
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| author | Anas Zahid Elizabeth L. Siegler Saad S. Kenderian |
| author_facet | Anas Zahid Elizabeth L. Siegler Saad S. Kenderian |
| author_sort | Anas Zahid |
| collection | DOAJ |
| description | T cells genetically engineered with chimeric antigen receptors (CART) have become a potent class of cancer immunotherapeutics. Numerous clinical trials of CART cells have revealed remarkable remission rates in patients with relapsed or refractory hematologic malignancies. Despite recent clinical success, CART cell therapy has also led to significant morbidity and occasional mortality from associated toxicities. Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) present barriers to the extensive use of CART cell therapy in the clinic. CRS can lead to fever, hypoxia, hypotension, coagulopathies, and multiorgan failure, and ICANS can result in cognitive dysfunction, seizures, and cerebral edema. The mechanisms of CRS and ICANS are becoming clearer, but many aspects remain unknown. Disease type and burden, peak serum CART cell levels, CART cell dose, CAR structure, elevated pro-inflammatory cytokines, and activated myeloid and endothelial cells all contribute to CART cell toxicity. Current guidelines for the management of toxicities associated with CART cell therapy vary between clinics, but are typically comprised of supportive care and treatment with corticosteroids or tocilizumab, depending on the severity of the symptoms. Acquiring a deeper understanding of CART cell toxicities and developing new management and prevention strategies are ongoing. In this review, we present findings in the mechanisms and management of CART cell toxicities. |
| first_indexed | 2024-04-24T15:33:23Z |
| format | Article |
| id | doaj.art-ac80b00c5bbb4b24b328a80995121ea8 |
| institution | Directory Open Access Journal |
| issn | 2590-0048 |
| language | English |
| last_indexed | 2024-04-24T15:33:23Z |
| publishDate | 2020-11-01 |
| publisher | SAABRON PRESS |
| record_format | Article |
| series | Clinical Hematology International |
| spelling | doaj.art-ac80b00c5bbb4b24b328a80995121ea82024-04-02T03:18:49ZengSAABRON PRESSClinical Hematology International2590-00482020-11-012410.2991/chi.k.201108.001CART Cell Toxicities: New Insight into Mechanisms and ManagementAnas ZahidElizabeth L. SieglerSaad S. KenderianT cells genetically engineered with chimeric antigen receptors (CART) have become a potent class of cancer immunotherapeutics. Numerous clinical trials of CART cells have revealed remarkable remission rates in patients with relapsed or refractory hematologic malignancies. Despite recent clinical success, CART cell therapy has also led to significant morbidity and occasional mortality from associated toxicities. Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) present barriers to the extensive use of CART cell therapy in the clinic. CRS can lead to fever, hypoxia, hypotension, coagulopathies, and multiorgan failure, and ICANS can result in cognitive dysfunction, seizures, and cerebral edema. The mechanisms of CRS and ICANS are becoming clearer, but many aspects remain unknown. Disease type and burden, peak serum CART cell levels, CART cell dose, CAR structure, elevated pro-inflammatory cytokines, and activated myeloid and endothelial cells all contribute to CART cell toxicity. Current guidelines for the management of toxicities associated with CART cell therapy vary between clinics, but are typically comprised of supportive care and treatment with corticosteroids or tocilizumab, depending on the severity of the symptoms. Acquiring a deeper understanding of CART cell toxicities and developing new management and prevention strategies are ongoing. In this review, we present findings in the mechanisms and management of CART cell toxicities.https://www.atlantis-press.com/article/125946348/viewCART cell therapyImmunotherapyCytokine release syndrome (CRS)Neurotoxicity |
| spellingShingle | Anas Zahid Elizabeth L. Siegler Saad S. Kenderian CART Cell Toxicities: New Insight into Mechanisms and Management Clinical Hematology International CART cell therapy Immunotherapy Cytokine release syndrome (CRS) Neurotoxicity |
| title | CART Cell Toxicities: New Insight into Mechanisms and Management |
| title_full | CART Cell Toxicities: New Insight into Mechanisms and Management |
| title_fullStr | CART Cell Toxicities: New Insight into Mechanisms and Management |
| title_full_unstemmed | CART Cell Toxicities: New Insight into Mechanisms and Management |
| title_short | CART Cell Toxicities: New Insight into Mechanisms and Management |
| title_sort | cart cell toxicities new insight into mechanisms and management |
| topic | CART cell therapy Immunotherapy Cytokine release syndrome (CRS) Neurotoxicity |
| url | https://www.atlantis-press.com/article/125946348/view |
| work_keys_str_mv | AT anaszahid cartcelltoxicitiesnewinsightintomechanismsandmanagement AT elizabethlsiegler cartcelltoxicitiesnewinsightintomechanismsandmanagement AT saadskenderian cartcelltoxicitiesnewinsightintomechanismsandmanagement |