Mount Sinai Researchers Identify a Potential Cancer Vaccine
Disguising cancer cells as bacterial cells provides new strategy for cancer vaccine.
Tumor cells engineered to resemble Salmonella trigger a robust immune response in mice, a discovery that could lay the groundwork for a viable cancer vaccine strategy in humans, according to researchers at Mount Sinai School of Medicine. The findings were published recently in Science Translational Medicine.
Tumors are able to grow because the immune system does not recognize tumor cells as a foreign threat to the body. However, the body does recognize and respond to bacteria. By masquerading the tumor cells as Salmonella bacteria, the researchers prompt the immune system into destroying the invading Salmonella.
The research team, led by Julie Magarian Blander, PhD, Associate Professor at the Immunology Institute and Director of the Innate Immunity Research Program at Mount Sinai School of Medicine, engineered melanoma and T-cell lymphoma cells to express a protein called flagellin, which is found in Salmonella and other bacteria. They then irradiated these tumor cells and used them as a cell-based vaccine.
Mice with tumors were injected with the vaccine, which set off an immune response clearing the tumor cells and preventing metastasis. The research team also vaccinated another group of mice, followed by an injection with just the tumor cells used to create the vaccine. These mice destroyed the tumor cells. The researchers further found that mice vaccinated with a combination of flagellin plus irradiated tumor cells were not protected against tumor development. The vaccine was only effective if the flagellin protein was expressed within the tumor cell itself.
“Our findings indicate that we may be able to create a human anticancer vaccine using irradiated tumor cells expressing flagellin,” said Dr. Blander. “This finding urges a reconsideration of the manner in which microbial component-based adjuvants are used in cancer immunotherapy clinical trials.”
Also relevant to designing optimal cancer vaccines was the researchers’ demonstration that protection from tumor growth after vaccination relied on the ability of flagellin to simultaneously engage two types of immune receptors, the Toll-like and Nod-like receptors, both of which were critical for mounting a lasting anticancer T cell immune response. The majority of cancer vaccines currently in clinical trials rely on targeting only Toll-like receptors. The Mount Sinai team’s discovery indicates that targeting both Toll-like and Nod-like receptors hold significant potential.
“Much of cancer immunotherapy research has focused on developing vaccines customized to the antigens expressed by a particular tumor type, a strategy which involves extensive effort in identifying these tumor-specific antigens,” Dr. Blander added. “Our study shows that manipulating tumor cells to express flagellin allows the immune system to target known and unknown antigens unique to tumor cells, and may eliminate the need for specific tumor antigen discovery.”
As with other autologous whole cell cancer vaccines, researchers are concerned about generating an autoimmune response in humans. Dr. Blander’s laboratory plans to assess whether the vaccine preferentially triggers a response to proteins specific to cancer cells and not healthy cells.
Dr. Blander said, “Our findings should encourage the incorporation of flagellin into existing vaccines based on tumor specific antigens; fusing these antigens to flagellin or expressing them together with flagellin in tumor cell lines or peripheral blood mononuclear cells.”
This work was supported by an American Cancer Society basic research scholar grant to Dr. Blander.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation’s top hospitals based on reputation, safety, and other patient-care factors. Of the top 20 hospitals in the United States, Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.
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