Listeria-based booster immune vaccine strategies improve protection against recurrent colorectal cancer

Colorectal cancer, pancreatic cancer, esophageal cancer, and gastric cancer-; some of the most deadly types of cancer-; the recurrence rate of cancer is high even after successful surgery and radiation therapy.

To combat these refractory cancers, researchers at Thomas University Jefferson, led by Dr. Adam Snook, an associate professor of pharmacology and treatment, instead said the patient’s immune system to prevent the cancer from recurring. Use what is essentially a vaccine to train. Vaccines usually use either a modified virus or a modified bacterium.

Currently, a new study from Dr. Snook’s lab shows that it is safe to use the viral and bacterial vaccine approaches together and is far more effective in combating cancer than either approach alone. Shown in animal model.

Vaccine platforms are not unique. However, no one has put together a vaccine that combines them. Still, it was then that I saw the immune response actually recover. “

Dr. Adam Snook, Associate Professor of Pharmacology and Experimental Treatment, Researcher at Sidney Kimmel Cancer Center – Jefferson Health

In a previous study, Dr. Snook and his team worked as a cancer vaccine backbone to train a patient’s immune system to identify and attack a unique colorectal cancer molecule called GUCY2C (pronounced GUCY2C). We used a modified version of a common virus known as adenovirus). This vaccine treatment, called Ad5.F35-GUCY2C, is currently in Phase II clinical trials.

The adenovirus-based vaccine approach stimulates a patient’s highly effective immune response, but the effect is not persistent. Vaccines often require additional doses to produce the best possible immune response. However, once introduced, the body becomes familiar with adenovirus and, as a result, does not produce the same type of immune response at additional doses. The body needed another type of booster for the primed immune system to continue to deliver cancer-fighting immunity.

Dr. Snook and his team turned to a bacterial-based vaccine approach using a modified format. Listeria monocytogenes It cannot cause illness in mice or humans. Unlike the adenovirus platform Listeria approach I’m not good at creating an immune response, but even with additional doses, it’s good at boosting the response.

In addition, “it is really good at infecting certain types of immune cells called antigen It presents cells that are important for producing an effective immune response against cancer, “says Dr. Snook.

At that time, they came up with the idea of ​​combining the two platforms. When researchers first stimulate the animal’s immune system with an adenovirus-based vaccine and then fortify it with a listeria-based vaccine, immune cells that attack cancer cells fire more than 15-fold in mice. did.

In a model of recurrent colorectal cancer that has spread beyond the colon to parts of the body, the combination vaccine approach reduced animal metastasis and increased survival, researchers said in a journal on June 23. Reported to npj vaccine..

“The combination of these two platforms actually worked much better than using either platform alone to create an immune response that targets cancer,” Dr. Snook said. say.

Vaccine strategies have also shown that they do not cause toxicity or inflammation in animals and that treatment is well tolerated without unintended effects.

The findings laid the foundation for the first time to see if this combination could prevent the patient from recurring cancer. The Pentagon recently awarded Dr. Snook and his colleague, Dr. Bavar Basir, MD, an assistant professor of oncology at Jefferson, a “team science” grant to incorporate the combination vaccine approach into Phase I clinical trials. Researchers are currently working on the production of the vaccine and will begin enrolling patients next year.

The one-two hit of the combo vaccine platform also affects other cancers and diseases such as HIV and malaria for which it was difficult to develop effective vaccine strategies.

“Such a platform is also very effective against these illnesses,” says Dr. Snook.