A Combination Cancer Vaccine Initiates Robust Immune Attack and Helps Form Long-Term Memory Against Tumors

Tuesday - May 30 2023, 02:33 UTC - 1 year ago

A cancer vaccine combining checkpoint blockade therapy and a STING-activating drug eliminates tumors and prevents recurrence in mice with little side effects and is even effective in cases with mutated STING gene.

MIT researchers have engineered a therapeutic cancer vaccine that targets the STING pathway, vital for immune response to cancer cells. This vaccine has shown significant potential in eliminating tumors, inhibiting metastasis, and preventing recurrence in mouse models of different cancers, with minimal side effects. The treatment is even effective in cases where the STING gene is mutated. The study also revealed an unexpected key role of CD4+ T cells in antitumor immunity.

Immune checkpoint blockade therapies have been revolutionary in the treatment of some cancer types, emerging as one of the most promising treatments for diseases such as melanoma, colon cancer, and non-small cell lung cancer.

While in some cases checkpoint blockade therapies elicit a strong immune response that clears tumors, checkpoint inhibitors do not work for all tumor types or all patients. Moreover, some patients who do experience an initial benefit from these therapies see their cancers recur. Only a small minority of patients treated with checkpoint blockade therapies see lasting benefits. Researchers have developed various combination therapy strategies to overcome resistance to checkpoint blockade therapies, with the STING pathway emerging as one of the most attractive lines of inquiry.

In a study published recently in the journal Advanced Healthcare Materials, a team of MIT researchers engineered a therapeutic cancer vaccine capable of restoring STING signaling and eliminating the majority of tumors in mouse models of colon cancer and melanoma, with minimal side effects. The vaccine also inhibited metastasis in a breast cancer mouse model and prevented the recurrence of tumors in cured mice.

"We have repurposed a naturally existing adaptor protein into a novel, dual-functional cancer vaccine that initiates and sustains an effective antitumoral immunity. The protein complex stimulated robust immune attack and helped form long-term memory against tumors in mouse models of colon cancer and melanoma," says Angela Belcher, the senior author of the study, a member of the Koch Institute for Integrative Cancer Research, and the head of MIT’s Department of Biological Engineering.

The study was led by MIT postdoc Yanpu He and conducted in collaboration with the laboratory of Paula Hammond, who is also a member of the Koch Institute, an MIT Institute Professor, and the head of MIT’s Department of Chemical Engineering. Other authors of the paper include Celestine Hong, Shengnan Huang, Justin Kaskow, Gil Covarrubias, Ivan Pires, and James Sacane.

Immune checkpoints are a key part of a system that helps the immune system tell the difference between the body’s own healthy cells and threats such as harmful bacteria or cancer cells. When checkpoint proteins on the surface of immune cells bind to partner proteins on other cells, the interaction gives rise to a signal that prevents T cells and other immune cells from mounting an attack. By presenting the same type of partner proteins, cancer cells can evade destruction by the immune system.