CAR-T (Chimeric Antigen Receptor T-cell Therapy)
Definition:
CAR-T is a form of cellular immunotherapy where a patient’s own T-cells are collected, genetically engineered to express a chimeric antigen receptor (CAR) that specifically targets a tumor-associated antigen (e.g., CD19 in B-cell ALL), expanded in the lab, and then reinfused into the patient to attack cancer cells.
Key Components
- Chimeric Antigen Receptor (CAR):
- Extracellular domain = antibody-derived fragment (scFv) → recognizes specific antigen (e.g., CD19, BCMA).
- Transmembrane + intracellular domains = provide activation signals (CD3ζ) + costimulatory domains (CD28, 4-1BB) for T-cell survival and proliferation.
- Patient’s T-cells:
Act as the effector cells after modification.
Process (Simplified)
- Leukapheresis → patient’s T-cells collected.
- Genetic modification (viral vector or CRISPR) to insert CAR gene.
- Ex vivo expansion → large numbers of CAR-T cells grown.
- Lymphodepletion chemotherapy (Fludarabine + Cyclophosphamide) to prepare host.
- Reinfusion of CAR-T cells → cells seek and destroy antigen-expressing cancer cells.
Indications (Oncology)
- Pediatric & young adult B-cell ALL (relapsed/refractory) → e.g., Tisagenlecleucel (Kymriah®).
- Relapsed/refractory DLBCL (axicabtagene, lisocabtagene).
- Multiple Myeloma (BCMA-targeted CAR-T: idecabtagene, ciltacabtagene).
Toxicities / Monitoring
- Cytokine Release Syndrome (CRS):
- Fever, hypotension, hypoxia.
- Managed with Tocilizumab (IL-6R blocker) ± corticosteroids.
- Immune Effector Cell–Associated Neurotoxicity Syndrome (ICANS):
- Confusion, aphasia, seizures, cerebral edema.
- Managed with corticosteroids (not tocilizumab).
- Prolonged cytopenias & infections (need antimicrobial prophylaxis).
- B-cell aplasia/hypogammaglobulinemia → IVIG replacement may be required.
In summary:
CAR-T = personalized, living immunotherapy that reprograms a patient’s T-cells to directly recognize and kill cancer cells, especially effective in relapsed/refractory pediatric and adult B-ALL.
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