A different immunotherapy target opens the door to new drugs

Immunotherapies have begun to be used effectively in cancer treatment. Clinically available immunotherapy drugs aim to activate T cells, the fighting cells of the immune system. Some research in recent years has focused on developing drugs that enable other immune system cells to target cancer as well. JCI Insightpublished a study suggesting that activating macrophages with specific antibodies may enable cancer cells to be destroyed effectively. Macrophages are among the cells playing a fundamental role in developing an immune response against cancer cells.

When macrophages recognize a cancer cell, they surround and destroy it. This process is called phagocytosis . Cancer cells have developed various resistance mechanisms to evade the immune response caused by macrophages. Through a series of experiments, researchers tried to understand how cancer cells become invisible to macrophages.

• The protein on the surface of cancer cells, CD47 , binds to the protein on the surface of macrophages, SIRPa , preventing macrophages from attacking cancer cells (left-hand diagram).
• The anti–SIRPa antibody developed prevented binding between cancer cells and macrophages, enabling macrophages to target the cancer cell (right-hand diagram). Researchers also administered the cancer drug rituximab alongside it, succeeding in stopping cancer cells more effectively.

SIRPa protein activity was also found to be very high in kidney cancer cells. Tumor growth was observed to be inhibited when the anti-SIRPa antibody was administered. In light of all these findings, the anti-SIRPa antibody was found to have a dual effect.

What does this study mean clinically?

• A new drug target has been discovered for immunotherapies, which hold great promise in modern cancer treatment.
• It sheds light on the development of new-generation drugs based on activating macrophages, another type of fighting cell in the immune system.