A3.2 Adoptive cellular therapies

Topic

Adoptive cell therapies involve transferring immune cells to a patient—cells that have been modified or expanded outside the body—thereby endowing them with a far greater capacity to eliminate tumors than they originally possessed. Unlike checkpoint inhibitors, which merely release the "brakes" on the patient's existing T cells, adoptive cell therapies introduce new effector cells with predefined properties, rather than relying on the patient's own T cells to activate spontaneously.

The quintessential example of adoptive cell therapy is the chimeric antigen receptor (CAR) T cell: the patient's own T cells are harvested and genetically modified to express an artificial receptor on their surface—the chimeric receptor, so named because it combines components from various natural receptors—capable of recognizing a specific tumor antigen with very high affinity. Other variants of adoptive cell therapy follow the same general logic of replacing or bolstering the immune system's effector cells, whether by expanding immune cells already present within the tumor or by utilizing other types of immune cells capable of directly killing tumor cells.

The underlying principle of these adoptive cell therapies is akin to control systems engineering: first, an effector cell is designed with a receptor that has very high affinity for a specific tumor antigen; next, the cell is produced in large quantities outside the patient's body; and finally, it is reinfused into the patient with the aim that, once inside the body, the cell will proliferate on its own and bring about massive tumor elimination. The cytotoxic capacity of a chimeric receptor T cell is far greater than that of a patient's endogenous T cell, and it offers an additional advantage: because the chimeric receptor directly recognizes the tumor antigen on the tumor cell surface, this modified T cell does not rely on the antigen-presentation system that tumor cells normally use to display antigens to endogenous T cells. Consequently, even if the tumor cell loses that antigen-presentation system—one of the most common ways tumors evade endogenous T cells—the chimeric receptor T cell continues to recognize it just the same.

Overall, this entire process—spanning the design of the chimeric receptor, its production outside the patient's body, and the subsequent massive elimination of the tumor within the patient without relying on the tumor cell's antigen-presentation system—is what gives adoptive cell therapies their advantage over other forms of immunotherapy. Instead of waiting for the patient's own effector cells to activate and recognize the tumor on their own, adoptive cell therapies provide the patient with effector cells that are already engineered and expanded, possessing a cytotoxic capacity ready to act the moment they are reinfused.

ID:2308