Skip to main content
Fig. 2 | Journal of Experimental & Clinical Cancer Research

Fig. 2

From: Emerging therapies for glioblastoma: current state and future directions

Fig. 2

General structure of CAR and CAR T-cell therapy. a Basic structure of T-cell receptor (TCR). The TCR comprise variable TCR-α and -β chains coupled to three dimeric signaling transduction modules CD3 δ/ε, CD3 γ/ε and CD3 ζ/ζ. T cell activation usually requires MHC matching. b Structure of 1st- 4th generation CARs. Chimeric antigen receptor (CAR) are fusion proteins consisting of an extracellular domain with a tumor-binding moiety, typically a single-chain variable fragment (scFv), followed by a hinge of varying length and flexibility, a transmembrane (TM) region, and one or more intracellular signaling domains associated with the T-cell signaling. First-generation CARs contain the stimulatory domain of CD3ζ, whereas second-generation CARs possess a co-stimulatory domain (typically CD28 or 4-1BB) fused to CD3ζ to ensure full activation. Third-generation CARs consist of two co-stimulatory domains linked to CD3ζ to maximize signaling activation. The first co-stimulatory domain is either a CD28 or a 4-1BB domain, with the second co-stimulatory domain consisting of either a CD28, a 4-1BB or a OX40 domain. The fourth-generation CARs, combine the second-generation CAR with the addition of various genes, including cytokines and co-stimulatory ligands, to enhance the tumoricidal effect of the CAR T cells. c Mechanisms of CAR-T therapy. CAR-T cells can produce an artificial T cell receptor that has high affinity to a tumor-specific surface antigen. BiTEs can redirect T cells to tumor cell surface antigens and activate T cells. Activated T cells release perforin and other granzymes through immunological synapses. These cytolytic proteins can form pores on tumor cell surface, and thus are endocytosed by tumor cells and then form endosomes and lyse tumor cells ultimately form endosomes in tumor cells and lyse tumor cells ultimately

Back to article page