Chimeric antigen receptor with integrated co-stimulatory domain (CAR (with specified co-stimulatory domain, e.g., CAR-CD28, CAR-4-1BB))

Chimeric antigen receptor with integrated co-stimulatory domain is an engineered synthetic receptor used in cellular immunotherapies, principally CAR-T cells. It consists of an extracellular antigen recognition domain (commonly a monoclonal antibody-derived single-chain variable fragment), a transmembrane region, and an intracellular domain that incorporates both a CD3ζ activation signaling motif and at least one co-stimulatory signaling domain (such as CD28, 4-1BB, ICOS, OX40, or CD27). The addition of the co-stimulatory domain(s) greatly enhances T cell proliferation, survival, and cytolytic function. Different co-stimulatory domains confer distinct functional properties and persistence to the engineered T cells, crucially impacting therapeutic efficacy and safety. These targets are central to FDA-approved immunotherapies for hematological malignancies and are undergoing active investigation in solid tumors and other diseases.

Other names

Chimeric antigen receptor (CAR) with co-stimulatory domainCAR-T cell receptor (with specific co-stimulation, e.g. CAR-4-1BB, CAR-CD28)CAR with integrated costimulatory domain

CARs with integrated co-stimulatory domains bind target antigen (e.g., CD19) via extracellular single-chain variable fragment (scFv). Engagement triggers T cell activation via intracellular CD3ζ signaling domain and provides co-stimulation through an integrated domain (commonly CD28, 4-1BB), leading to T cell proliferation, cytokine secretion, and cytotoxic activity against antigen-bearing tumor cells. Enhanced persistence, expansion, and anti-tumor efficacy compared to first-generation CARs without co-stimulatory domains.