Autologous CAR T cell therapies are created from the patient’s own T cells. The production processes used to create CAR T cell therapies are specific to each product, which makes each CAR T cell therapy different.
CAR T cell therapy involves the infusion of T cells that have been genetically engineered to express a chimeric antigen receptor (CAR) to reprogram the T cells. The CAR combines the specificity of a monoclonal antibody with the cytotoxic and memory functions of T cells.
CAR specificity comes from the extracellular domain, which is derived from the antigen-binding site of a monoclonal antibody.
Since CAR T cells carry their own co-stimulatory signaling, they may be less susceptible than unmodified T cells to the negative regulation from tumors.
Anatomy of a chimeric antigen receptor (CAR)
2.Extracellular Antigen-binding Domain
Extracellular Spacer/Hinge RegionConnecting sequence between the extracellular antigen-binding domain and the transmembrane domain. Differences in the length and flexibility of the resulting CAR can affect CAR T cell function.
4.Intracellular Co-stimulatory Domain
Intracellular Signaling DomainThe intracellular portion of the CAR also includes the signaling domain, typically the TCR complex CD3 zeta.
How CAR T cell therapy is thought to work
Evidence suggests that CAR T cell therapies stimulate a T cell response against antigen-expressing cells, including normal and malignant cells. The external targeting domain binds to the antigen, activating the CAR T cell. Once activated, CAR T cells release cytokines and other soluble mediators that may play a role in the killing of antigen-expressing target cells and normal cells.
CAR T cell expansion and persistence
Expansion and persistence of CAR T cells in the body are linked to several important factors.
Adapted from Kawalekar OU, et al. Immunity. 2016;44:380-390.
Co-stimulatory signaling is thought to influence T cell expansion, metabolic profile, persistence, and subset composition.
- Higher proportion of effector memory T cells, which rapidly differentiate into short-lived effector T cells
- Short persistence
- Higher proportion of central memory T cells, which are less differentiated and more able to proliferate than effector memory cells
- Slower, sustained effector function
- Greater persistence
T cell selection and composition
CD4 and CD8 T cells are functionally distinct subsets that differ in their ability to proliferate and persist in the body.
Ex vivo expansion
CAR T cells are expanded, or grown, outside the body to an appropriate therapeutic dose.
Explore more with the informational modules of CAR T Academy.
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