Chimeric Antigen Receptor (CAR)-T Cells are a Type of Genetically Modified Autologous Immunotherapy (Oncoimmunology, 2012) [MEDLINE] (Cancer Discov, 2013) [MEDLINE]
Technique
Collection of Patient’s Own (Autologous) T-Cells from the Blood
Modification of T-Cells Ex Vivo to Express a Tumor Antigen-Specific CAR (Antigen-Binding Domain from a B-Cell Receptor Which is Fused to the Intracellular Domain of a CD3 TCR, CD3-Zeta)
Ex Vivo Expansion of the Cells
Reinfusion of Cells Back into the Patient
Recognition of a Specific Tumor/Cell Surface Antigen Activates the T-Cell Response (Independent of MHC Recognition)
Modifications Which Can Further Enhance CAR-T Cell Effector Functions
Co-Expression of Intracellular Costimulatory Domains (CD28, 4-1BB [CD137], etc)
Case Reports with CD19 CAR-T Therapy (Front Immunol, 2022) [MEDLINE]
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Clinical
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CD19 CAR-T Cell Therapy Induced Immunotherapy Associated Interstitial Pneumonitis: A Case Report. Front Immunol. 2022 Jan 27;13:778192. doi: 10.3389/fimmu.2022.778192 [MEDLINE]
Background
Chimeric antigen receptor-modified T cells (CAR-T) targeting CD19 has produced a high durable response in refractory or relapsed diffuse large B-cell lymphoma. Besides well-known cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome during CAR-T cell therapy, there were several rarely encountered fatal complications.
Case Report
A 63-year-old male patient with refractory EBV-positive diffuse large B-cell lymphoma, developed interstitial pneumonitis with prolonged hypoxemia at 16 weeks after CD19 CAR-T cell therapy. There was no evidence of CRS and any infections. The patient recovered after intravenous immunoglobulin without tocilizumab or glucocorticoid administration. Now he is still in remission without interstitial pneumonitis 3 years after CAR-T cell therapy.
Conclusion
This is the first report of immunotherapy-associated interstitial pneumonitis after CAR-T cell therapy. Our finding suggested the importance of careful follow-up and proper treatments for immunotherapy-associated pneumonitis in the CAR-T cell therapy schedule.
Imaging the Side Effects of CAR T Cell Therapy: A Primer for the Practicing Radiologist. Acad Radiol. 2023 Nov;30(11):2712-2727. doi: 10.1016/j.acra.2023.04.004 [MEDLINE]
Chimeric antigen receptor (CAR) T cell therapy is a revolutionary form of immunotherapy that has proven to be efficacious in the treatment of many hematologic cancers. CARs are modified T lymphocytes that express an artificial receptor specific to a tumor-associated antigen. These engineered cells are then reintroduced to upregulate the host immune responses and eradicate malignant cells. While the use of CAR T cell therapy is rapidly expanding, little is known about how common side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) present radiographically. Here we provide a comprehensive review of how side effects present in different organ systems and how they can be optimally imaged. Early and accurate recognition of the radiographic presentation of these side effects is critical to the practicing radiologist and their patients so that these side effects can be promptly identified and treated.
References
General
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Pharmacology
How do CARs work?: Early insights from recent clinical studies targeting CD19. Oncoimmunology. 2012 Dec;1(9):1577-1583 [MEDLINE]
The basic principles of chimeric antigen receptor design. Cancer Discov. 2013 Apr;3(4):388-98 [MEDLINE]
