Nowadays, immunotherapy has shown great potential in treating human cancer, but it is not effective for all tumor types and only works for less than 3% of pancreatic ductal adenocarcinoma (PDAC) patients. In a study published in the international journal Frontiers in Immunology titled “Intracellular Salmonella delivery of an exogenous immunization antigen refocuses CD8 T cells against cancer cells, eliminates pancreatic tumors and forms antitumor immunity”, scientists from Massachusetts University and other institutions demonstrated theoretically that a protein antigen from a childhood vaccine may be transported into malignant tumor cells, thereby reprogramming the body’s immune system to fight against cancer and effectively inhibit cancer recurrence.
This intracellular bacterial delivery system, based on the toxic form of Salmonella, can release drugs (in this case, vaccine antigens) after entering solid tumor cancer cells. Professor Neil Forbes, the researcher, stated that as a ready-made immunotherapy, this bacterial system holds promise for effectively treating a range of cancers and provides new hope for difficult-to-treat cancers such as liver cancer, metastatic breast cancer, and pancreatic cancer.
Researchers believe that if the immune system could be targeted specifically against cancer through immunizations, there may be hope for eradicating cancer. However, since cancer cells do not display viral molecules on their surfaces, the challenge is whether a specific molecule could be introduced into cancer cells using Salmonella bacteria as a delivery system, prompting the immune system to attack the cancer cells as it would an invading pathogen. To test the effectiveness of this immunotherapy, researchers, including Professor Neil Forbes, genetically engineered Salmonella bacteria for intracellular delivery of ovalbumin, a protein antigen, into pancreatic tumor cells in mice that had been vaccinated with ovalbumin. They found that the ovalbumin dispersed within the culture medium and the matrix of tumor cells.
Subsequently, the ovalbumin protein induced an antigen-specific T-cell response in the cytoplasm to attack cancer cells. This therapy cleared 43% of established pancreatic tumors, improved the survival rate of mice, and prevented tumor re-implantation. Currently, researchers have observed 3 out of 7 mice in a pancreatic cancer model achieving remission. They are incredibly excited about this result, as this strategy clearly extends the survival rate of cancerous mice. Researchers attempted to reintroduce pancreatic tumors in immunized mice and found that no tumor growth occurred in the mice’s bodies. This suggests that mice not only developed immunity to ovalbumin protein but also to cancer itself, as their immune systems have learned that tumors have immunogenic properties. The researchers are currently further studying to elucidate how this process occurs.
In the initial studies, researchers found that injecting modified Salmonella bacteria into the bloodstream effectively treated liver tumors in mice. This finding has also been confirmed and expanded upon in current research on pancreatic tumors. Before clinical trials can begin, researchers have replicated the experiments in other animal models and optimized the intracellular delivery of Salmonella to ensure its safety for use in humans. The primary focus of the research will be liver cancer, followed by pancreatic cancer.
Finally, the researchers state that the response observed in immunosuppressed tumor models reveals the potential of this therapy for treating tumors that are unresponsive to checkpoint inhibitors. In a clinical setting, an intracellular Salmonella delivery system may be used to transport protein antigens derived from childhood vaccines, thereby reprogramming the pre-existing T cell immunity and potentially combating tumors. As an existing treatment approach, this unique bacterial system holds promise for helping to treat a range of human cancers.