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State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses.
Meir, Juliet; Abid, Muhammad Abbas; Abid, Muhammad Bilal.
  • Meir J; Department of Medicine, Westchester Medical Center, Valhalla, New York.
  • Abid MA; Department of Hematopathology & Microbiology, The Aga Khan University Hospital, Karachi, Pakistan.
  • Abid MB; Divisions of Infectious Diseases and Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: bilal_abid@hotmail.com.
Transplant Cell Ther ; 27(12): 973-987, 2021 12.
Article in English | MEDLINE | ID: covidwho-1492350
ABSTRACT
Chimeric antigen receptor T cell (CAR-T) therapy has shown unprecedented response rates in patients with relapsed/refractory (R/R) hematologic malignancies. Although CAR-T therapy gives hope to heavily pretreated patients, the rapid commercialization and cumulative immunosuppression of this therapy predispose patients to infections for a prolonged period. CAR-T therapy poses distinctive short- and long-term toxicities and infection risks among patients who receive CAR T-cells after multiple prior treatments, often including hematopoietic cell transplantation. The acute toxicities include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. The long-term B cell depletion, hypogammaglobulinemia, and cytopenia further predispose patients to severe infections and abrogate the remission success achieved by the living drug. These on-target-off-tumor toxicities deplete B-cells across the entire lineage and further diminish immune responses to vaccines. Early observational data suggest that patients with hematologic malignancies may not mount adequate humoral and cellular responses to SARS-CoV-2 vaccines. In this review, we summarize the immune compromising factors indigenous to CAR-T recipients. We discuss the immunogenic potential of different SARS-CoV-2 vaccines for CAR-T recipients based on the differences in vaccine manufacturing platforms. Given the lack of data related to the safety and efficacy of SARS-CoV-2 vaccines in this distinctively immunosuppressed cohort, we summarize the infection risks associated with Food and Drug Administration-approved CAR-T constructs and the potential determinants of vaccine responses. The review further highlights the potential need for booster vaccine dosing and the promise for heterologous prime-boosting and other novel vaccine strategies in CAR-T recipients. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Chimeric Antigen / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Transplant Cell Ther Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Chimeric Antigen / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Transplant Cell Ther Year: 2021 Document Type: Article