The Design of a Chimeric Antigen Receptor

Cameron J. Turtle, MD, PhD, Assistant Member, Fred Hutchinson Cancer Research Center, Assistant Professor, University of Washington, discusses the design of a chimeric antigen receptor (CAR).

There are multiple ways to design a CAR and several components need to be considered: single-chain variable fragments (scFv), intracellular costimulatory and signaling molecules, and transmembrane domains of the spaces in between. In looking at different studies in mice or in the lab, one can see difference in the effects of different types of CARs.

In the case of a new target tumor antigen and a new scFv, optimization studies must take place to determine the right parameters for that tumor antigen. Tumor antigens may even differ in the type of cells being engineered or the type of patients being treated.

Clinical Pearls

Turtle says that not one design will be optimal for every type of CAR.

• Components to a CAR include: scFv, intracellular costimulatory and signaling molecules, and the transmembrane domains of the spaces
• In the case of a new target tumor antigen and a new scFv, optimization studies must take place to determine the right parameters
• Not one design will be optimal for every type of CAR