A lab engineered receptor designed to bind certain proteins, such as surface proteins on cancer cells, that is added to immune cells for immunotherapy strategies such as directing T cells to fight cancer.
The first CAR-T treatment was approved by the FDA in 2017 and there are several in clinical trials. CAR-T has been successful in treating hematological malignancies. US FDA approved CAR-T therapies include CD19-targeting CAR-T cells, tisagenlecleucel (Kymriah-Novartis) in leukemia and lymphoma and axicabtagene ciloleucel (Yescarta – Kite) in lymphoma. Challenges to CAR-T including toxicity due to attacking non-cancer cells, "clonal escape" due to diversity of cancer cells, dosing, immunosuppression (turning off) of the T-cells, and T-cell apoptosis (cell death).
Treating solid tumors with CAR-T faces challenges including a lack of truly tumor-specific target antigens. The immunosuppressiveness of the tumor microenvironment (TME) of solid tumors also prevents effective anti-tumor immune responses. Components of the immunosuppressive TME contains includes physical barriers, such as a dense extracellular matrix; dysfunctional epithelial cells; metabolic checkpoints, such as hypoxia and immunological barriers, such as immunosuppressive cytokines/molecules and immunosuppressive immune cells.