Biologic
RCSB PDB 8HXQ
Ciltacabtagene autoleucel
Carvykti
- Mechanism of action
- Autologous anti-BCMA CAR-T cell therapy
- In plain language
- Reprograms a patient's own immune cells, using a llama-derived, dual-pronged targeting piece, to hunt down and destroy myeloma cells carrying the BCMA marker.
- How it works
- Ciltacabtagene autoleucel is an autologous chimeric antigen receptor (CAR) T-cell therapy directed against B-cell maturation antigen (BCMA), a protein expressed on malignant and normal plasma cells. A patient's T cells are collected by leukapheresis and genetically modified ex vivo via transduction with a replication-incompetent lentiviral vector encoding the CAR transgene. The CAR's antigen-recognition domain is built from two BCMA-targeting, llama-derived single-domain (heavy-chain-only) antibodies arranged to bind two distinct epitopes on BCMA simultaneously, conferring high avidity — a biepitopic design that differs structurally from the single scFv binding domains used in most other CAR-T products. This binding domain is fused to a 4-1BB costimulatory domain and a CD3-zeta signaling domain. After ex vivo expansion, the engineered cells are reinfused into the patient following lymphodepleting chemotherapy, and redirect the patient's T cells to recognize and eliminate BCMA-expressing myeloma cells independent of MHC restriction.
- Therapeutic applications
- Per FDA-approved labeling, CARVYKTI is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. CARVYKTI received initial U.S. approval in 2022 for a narrower population (four or more prior lines of therapy); the indication was expanded in April 2024, based on the CARTITUDE-4 trial, to the current earlier-line population.
- Class
- CAR-T cell therapy
- Therapeutic area
- Oncology (multiple myeloma)
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