CAR-T — oncology-focused definition
CAR-T (Chimeric Antigen Receptor T-cell) therapy is a type of immunotherapy in which a patient’s own T cells are genetically engineered to express a synthetic receptor that targets a specific tumor antigen.
Mechanism of Action:
- T cell collection: Patient’s T cells are harvested via leukapheresis.
- Genetic modification: T cells are engineered to express a chimeric antigen receptor (CAR) that recognizes a tumor-specific antigen (e.g., CD19).
- Expansion: Modified T cells are multiplied in the lab.
- Infusion: CAR-T cells are reinfused into the patient to recognize and kill tumor cells.
- The CAR combines:
- Extracellular antigen-binding domain (usually from a monoclonal antibody)
- Transmembrane domain
- Intracellular T-cell activation domain (CD3ζ and co-stimulatory domains like CD28 or 4-1BB)
Clinical relevance:
- Approved indications (examples):
- B-cell malignancies: CD19+ acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL)
- Multiple myeloma: BCMA-targeted CAR-T
- Advantages:
- Highly targeted and effective in refractory or relapsed disease
- Can produce long-term remission in some patients
- Toxicities / adverse effects:
- Cytokine release syndrome (CRS) → fever, hypotension, hypoxia
- Immune effector cell–associated neurotoxicity syndrome (ICANS) → confusion, seizures, cerebral edema
- B-cell aplasia (if CD19-directed therapy) → hypogammaglobulinemia
Key takeaway:
CAR-T therapy is a personalized immunotherapy that engineers T cells to target tumor-specific antigens, providing potent and potentially curative therapy for refractory hematologic malignancies, but requiring careful monitoring for CRS, neurotoxicity, and immunodeficiency.
Synonyms
CAR T-Cell Therapy, CAR T-Cell