CAR-T Cell Therapy (Chimeric Antigen Receptor T-Cell) for Cancer Immunotherapy — Regenerative Therapies
Patient's T-cells genetically engineered with chimeric antigen receptors to target and kill cancer cells. 7 FDA-approved products.
Overview
Chimeric Antigen Receptor T-cell (CAR-T) therapy is a revolutionary cancer immunotherapy in which patient's own T-cells are genetically engineered to express synthetic receptors that recognize specific tumor surface antigens. The CAR construct combines an extracellular antigen-binding domain, a transmembrane domain, and intracellular signaling domains (CD3-zeta + CD28 or 4-1BB). As of 2025, 7 CAR-T products are FDA-approved: Kymriah (tisagenlecleucel - B-ALL/DLBCL), Yescarta (axicabtagene ciloleucel - LBCL), Tecartus (brexucabtagene autoleucel - MCL/ALL), Breyanzi (lisocabtagene maraleucel - LBCL), Abecma (idecabtagene vicleucel - myeloma), Carvykti (ciltacabtagene autoleucel - myeloma), and Aucatzyl (obecabtagene autoleucel - B-ALL, 2024). Over 1,700 clinical trials are registered globally targeting solid tumors, using allogeneic designs, and incorporating CRISPR enhancements.
Indications
- B-cell acute lymphoblastic leukemia (B-ALL) - relapsed/refractory
- Diffuse large B-cell lymphoma (DLBCL) - relapsed/refractory
- Follicular lymphoma - relapsed/refractory
- Mantle cell lymphoma - relapsed/refractory
- Multiple myeloma (BCMA-targeted) - relapsed/refractory
- Large B-cell lymphoma (including PMBCL, HGBCL)
- Solid tumors (investigational: GD2, mesothelin, HER2, EGFRvIII targets)
Mechanism of Action
Patient undergoes leukapheresis to collect PBMCs. T-cells isolated and activated using anti-CD3/CD28 beads in the presence of IL-2 or IL-7/IL-15
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Tisagenlecleucel (Kymriah) | 0.2-5 x 10^8 CAR+ T-cells | Single infusion | IV infusion for B-ALL (Kymriah) - weight-based dosing for pediatric patients |
| Axicabtagene ciloleucel (Yescarta) | 2 x 10^6 CAR+ T-cells/kg | Single infusion | IV infusion for LBCL (Yescarta) - max 2 x 10^8 total cells |
| Ciltacabtagene autoleucel (Carvykti) | 0.5-1 x 10^6 CAR+ T-cells/kg | Single infusion | IV infusion for multiple myeloma (Carvykti) - BCMA-targeted |
Evidence Grade
GRADE C
Safety & Contraindications
- Cytokine release syndrome (CRS): occurs in 50-90% of patients, grade 3-4 in 10-25%
- Immune effector cell-associated neurotoxicity syndrome (ICANS): confusion, seizures, cerebral edema
- B-cell aplasia and hypogammaglobulinemia: lifelong consequence of CD19-targeted therapies
- Prolonged cytopenias: neutropenia, thrombocytopenia lasting weeks to months
- FDA class-wide REMS required
- Secondary T-cell malignancies: FDA investigating reports of CAR-T-related T-cell lymphomas
- Tumor lysis syndrome risk in high tumor burden patients
- Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)
- Manufacturing time: 3-5 weeks - patient may deteriorate
- Cost: $373,000-$475,000 per treatment (before hospitalization costs)
- Limited to REMS-certified treatment centers