What is CAR-T Cell Therapy?
CAR (Chimeric Antigen Receptor) T-cell therapy deploys the patient's immune cells to fight cancer. Even though the concept had been coined early in the 1980s, the therapy was only recently available to some types of blood cancer patients. The FDA approved the first two of the class of treatment in 2017: Novartis' Kymriah and Gilead's Yescarta. With many more similar therapies in the pipeline (Juno, Cellectis, etc.), CAR T-cell therapy has hit its prime time.
Schematic of the treatment process with chimeric antigen receptor (CAR) T cells.
(1) Isolation of peripheral T cells from patient via apheresis.
(2) Transfection of T cells with a lentivirus containing genes for CAR directed against the tumor target antigen: binding of virus to T-cell membrane, fusion of virus with cell membrane, reverse transcription, DNA integration, and transcription/protein expression of CAR genes, and insertion of CAR into cell membrane.
(3) Adoptive transfer of autologous CAR-T cells via infusion with or without prior lymphodepleting conditioning.
(4) Patient monitoring for treatment response, and for persistence of CAR-T cells.
The protocol of the CAR T cell therapy is illustrated in the schematic: active T cells were first collected from patients through a special medical process called apheresis. Afterwards is the core of the technology and where the innovations apply. Scientists engineer the T cells genetically to have the cells present the chimeric antigen receptors on cell surface. Finally, these engineered T cells were infused back to the patients. Those CAR T cells would proliferate in patients, and mount attacks specific to the patient's particular cancer. There is also approach that sources T cells from donors other than the patient, or "off-the-shelf" CAR T cells, but it is still under investigation.