Targeting both immune system branches could be key for cancer immunotherapy

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While most cancer immunotherapies target one branch of the immune system, a combination therapy that activates both immune subsystems could be the key to defeating aggressive cancers.

MIT researchers used a combo of four different treatments to trigger both the adaptive and innate immune systems in a coordinated attack that resulted in the “complete disappearance” of large, aggressive tumors in mice, according to a statement. The strategy could be used to tackle the suppressive effect that tumors often have on the immune system.

The innate immune system comprises nonspecific defenses, including antimicrobial peptides, while the adaptive immune system deploys immune cells that target specific antigens. MIT professors Darrell Irvine and Dane Wittrup were working on separate therapies, each targeting one of the two immune subsystems, when they realized their approaches might work better in tandem.

"We had this really good lymph-node-targeting vaccine that will drive very strong adaptive immunity, and they had this combination that was recruiting innate immunity very efficiently," Irvine said in the statement. "We wondered if we could bring these two together and try to generate a more integrated immune response that would bring together all arms of the immune system against the tumor."

The resulting treatment comprises an antibody and a vaccine that target the tumor, the signaling molecule IL-2 and a molecule that inhibits PD-1, according to the statement. The antibodies trigger the recruitment of immune cells that help activate T cells, while the vaccine causes T cells to multiply. IL-2 further drives the proliferation of T cells and the PD-1 inhibitor helps the T cells to be active for longer.

They tested the combo therapy in mice that had been implanted with melanoma, lymphoma or breast cancer. The treatment “completely cleared” about 75% of the tumors, according to the statement. Six months after initial treatment, the researchers injected the mice with tumor cells, finding that they were able to completely eradicate the tumor cells.

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