immunotherapy that triggers the immune system when bound

The protein, CAR19 (Chimeric Antigen Receptor to CD19) is a synthetic transmembrane receptor. It has the capability of triggering immune-cell activation when bound by CD19. B cells express CD19 on their surface. CAR19 can be used therapeutically to help the immune system seek and then destroy B cells that have become cancerous as in some Leukemias and Lymphomas.

The CAR-19 protein is produced by the genetic payload delivered by the CAR-T therapies named Kymriah & Yescarta.

Diagram of the six main features of CAR19

The CD8 signal sequence ensures the protein is exported to the surface of the cell. The CD19-scFV binds the CD19 protein found on B-cells. The CD8-Hinge domain extends the binding region off of the surface of the cell. The CD8 transmembrane domain ensures the protein is anchored to the cell surface. The CD137 intracellular domain is a costimulatory domain that enhances activation of the immune system. And the CD3ζ intracellular domain is the primary stimulation domain that activates the immune system. Together these domains, when expressed in a T-cell, act to activate its immunological response when it is in the presence of another cell that is expressing CD19.

Currently there are ~100 different CARs with variously modified domains in trials with the FDA for various diseases including Myeloma, ALL, CLL, NHL, breast cancer, ovarian, and various other cancers.



Abate-Daga & Davila (2016)