Some of the deadliest cancers such as colorectal, pancreatic, esophageal, and stomach cancers have high recurrence rates where the cancer comes back even after surgery or radiation treatment. Now, new research in animal models by scientists at Thomas Jefferson University demonstrates that using viral and bacterial vaccine approaches together is safe and effective at fighting treatment-resistant cancer than either approach by itself.

Their findings are published in the journal npj Vaccines in a paper titled, “Prime-Boost Immunization with Chimeric Adenoviral (Ad5.F35) and Listeria Vectors is a Safe and Effective Strategy for Cancer Immunotherapy.”

“Strategies to augment immunity to self/neoantigens expressed by cancers are urgently needed to expand the proportion of patients benefiting from immunotherapy, particularly for GI cancers where only a fraction of patients respond to immunotherapies,” wrote the researchers. “However, current vaccine strategies are limited by poor immunogenicity, pre-existing vector-specific immunity, and vaccine-induced vector-specific immunity. Here, we examined a prime-boost strategy using a chimeric adenoviral vector (Ad5.F35) that resists pre-existing immunity followed by recombinant Listeria monocytogenes (Lm) to amplify immunity to the GI cancer antigen GUCY2C.”

To combat treatment-resistant cancers, the scientists led by Adam Snook, PhD, an associate professor of pharmacology and experimental therapeutics, used vaccines to train patients’ immune systems to keep the cancer from coming back.

“The vaccine platforms are not unique,” explained Snook who is also a researcher at the Sidney Kimmel Cancer Center – Jefferson Health. “But nobody’s put them together into a combination vaccine, yet that’s when we saw the immune response really take off.”

Snook and his team previously used a modified form of adenovirus as the backbone of a cancer vaccine that trains patients’ immune systems to identify and attack a unique colorectal cancer molecule called GUCY2C. This vaccine treatment, dubbed Ad5.F35-GUCY2C, is currently in Phase II clinical trials.

The adenovirus-based vaccine approach stimulates an effective immune response in patients. However, the effect doesn’t last. To create the best possible immune response, vaccines often require additional doses. The scientists turned to a bacteria-based vaccine approach using a modified form of Listeria monocytogenes that is unable to cause illness in mice or people.

The scientists used the adenovirus-based vaccine to first prime the animals’ immune systems and then later boosted them with the Listeria-based vaccine.

In a model of recurrent colorectal cancer, the combination vaccine approach reduced metastases and increased survival in the animals.

“Combining these two platforms together actually worked way, way better than either platform alone for creating an immune response targeting the cancer,” Snook said.

The vaccine strategy also did not produce toxicity or inflammation in the animals indicating that the treatment was well-tolerated without unintended effects.

The findings have laid the groundwork to examine for the first time whether this combination could prevent cancers from coming back in patients. The one-two hit of the combo vaccine platform also has implications for other cancers and even diseases such as HIV and malaria, where effective vaccine strategies have been difficult to produce.

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