Proof-of-principle study shows immunity gained from routine vaccines has cancer-fighting potential


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Bacterial delivery of ovalbumin induces a specific CD8 T cell response. Credit: Frontiers in Immunology (2023). DOI: 10.3389/fimmu.2023.1228532

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Bacterial delivery of ovalbumin induces a specific CD8 T cell response. Credit: Frontiers in Immunology (2023). DOI: 10.3389/fimmu.2023.1228532

A team at the University of Massachusetts Amherst has demonstrated “theoretically” that a protein antigen from a childhood vaccine could be used to refocus the body’s immune system against cancer, effectively stopping it and preventing its recurrence. Can be delivered into malignant tumor cells.

Bacteria-based intracellular delivery (ID) systems use a non-toxic form of Salmonella that releases a drug, in this case a vaccine antigen, once it is inside a solid tumor cancer cell.

“As an off-the-shelf immunotherapy, this bacterial system has the potential to be effective in a wide range of cancer patients,” senior author Neil Forbes, professor of chemical engineering, wrote in a paper published Thursday, Oct. 5. Is. Frontiers in Immunology,

The research, conducted in the Forbes Lab at the Institute for Applied Life Sciences (IALS), holds promise for tackling difficult-to-treat cancers, including liver, metastatic breast and pancreatic tumors.

UMass Amherst has applied for a patent that will be licensed to Ernest Pharmaceuticals, an IALS startup co-founded by Forbes, first author Vishnu Raman, and bioengineer Nelle Van Dessel, who developed the delivery system as a post-doctoral researcher in the Forbes lab. did. They plan to seek FDA approval in an effort to begin clinical trials within a few years.

Forbes explains, “The idea is that everyone is vaccinated against multiple things, and if you can take that vaccination and target it toward a cancer, you can use it to eliminate cancer.” Can.” “But cancer obviously won’t display viral molecules on its surface. So the question was could we use Salmonella to get a molecule inside a cancer cell and then have the immune system attack that cancer cell as if Was that an attacking virus?”

To test their theory that this immune therapy might work, Forbes and team genetically engineered ID Salmonella to deliver ovalbumin (chicken egg protein) into the pancreatic tumor cells of mice, which were immunized with an ovalbumin ‘vaccine’. Was immunized. The researchers showed that ovalbumin diffuses into the cytoplasm of cells both in culture and in tumors.


Credit: University of Massachusetts Amherst

Ovalbumin then initiated an antigen-specific T-cell response in the cytoplasm that attacked the cancer cells. The paper said the therapy cleared 43% of established pancreatic tumors, increased survival and prevented tumor re-implantation.

“We have completely cured three of the seven pancreatic mouse models,” Forbes says. “We’re really excited about it; it dramatically increased survival.”

The team then attempted to reintroduce pancreatic tumors into immunized mice. The results were extremely positive. “No tumors grew, which means the mice had developed immunity not only to ovalbumin but also to the cancer,” Forbes says. “The immune system has detected that the tumor is an immunogenic one. I’m doing further work to find out exactly how this is happening.”

In preliminary research, the team previously showed that injecting modified Salmonella into the bloodstream effectively treated liver tumors in mice. They further complemented their findings with current research on pancreatic tumors.

Before clinical trials begin, researchers will repeat the experiments on other animals and refine the ID Salmonella strain to ensure its safety for use in humans. Liver cancer will be the first target, followed by pancreatic cancer.

“This is not just an academic exercise,” says Forbes, whose grandfather—for whom Ernest Pharmaceuticals is named—died of prostate cancer. “I’m actually trying to create a cancer therapy.”

more information:
Vishnu Raman et al, Intracellular Salmonella delivery of an exogenous vaccination antigen refocuses CD8 T cells against cancer cells, eliminates pancreatic tumors and induces antitumor immunity, Frontiers in Immunology (2023). DOI: 10.3389/fimmu.2023.1228532

Journal Information:
Frontiers in Immunology

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