Staging
CAR T-cell generations
CAR T-cell generations classify receptor constructs by the number of intracellular costimulatory domains added to the activation signal.
Also called: second- and third-generation constructs
Stages
- 1
First generation
CD3 zeta activation domain only, with no costimulatory domain.
- 2
Second generation
Activation domain plus one costimulatory domain, such as CD28 or 4-1BB.
- 3
Third generation
Activation domain plus two or more costimulatory domains.
Judged onThe intracellular signaling and costimulatory domains in the chimeric antigen receptor construct
This naming system distinguishes CAR designs by the signaling modules inside the engineered receptor. The first-generation design provides an activation signal through CD3 zeta, while later designs add costimulatory domains such as CD28 or 4-1BB to support T-cell activity. It is used when comparing engineered T-cell therapies. The generation describes receptor architecture, not a treatment stage for the patient.