The purpose of this blog is to increase exposure to the growing field of bacterial based cancer therapy and introduce its recent advances to the broader scientific community. This novel method of treating cancer uses infectious microbes that have been genetically engineered to exhibit direct oncolysis or activate the immune system.
There are four distinct advantages of bacterial based cancer therapy over current immunotherapies:
- Bacteria selectively invade and colonize solid tumors at extremely high ratios over the normal tissue of colonization (liver and spleen). Because such bacteria are facultative intracellular organisms and seek out hypoxic areas, it is hypothesized that Salmonella are naturally drawn to colonize tumors because solid primary and metastatic tumor deposits are thought to be warmer and more hypoxic than normal host tissue.
- Bacteria stimulate the innate immune system. Many types of bacteria are able to colonize and convert the tumor microenvironment through proinflammatory responses. This alters the immunosuppressive nature of these tumors and converts them to immune stimulating.
- Bacteria have the ability to host large amount of foreign DNA. Bacterial vectors can therefore be genetically engineered to produce cytotoxic proteins within the tumor. They can also be genetically altered to attenuate the strain and reduce systemic toxicity.
- Bacteria compete with the host tumor tissue for nutrients following colonization. This accumulation of bacteria within the tumor can cause direct oncolysis.
Due to bacteria’s increased propensity to the tumor microenvironment, their immunostimulatory nature, and their ability to host large amounts of foreign DNA, they become an attractive candidate for delivery of cytotoxic proteins to the tumor microenvironment in order to create a desired anti-cancer immune response.
Salspera has emerged as a leader in the field of microbial immunotherapy. The company has created a platform of orally administered microbial immunotherapies, genetically engineered to eliminate pathogenicity and express various cytokines and cytotoxic proteins within the tumor microenvironment. One of these therapies is Saltikva, an orally administered, unique, non-toxic cancer therapeutic that acts synergistically with conventional chemotherapy. Saltikva is an attenuated Salmonella Typhimurium containing the gene for human IL-2. (Salmonella-IL2). Saltikva is a Salmonella based cancer therapeutic that has been genetically altered so it is incapable of causing any disease and is unable to mutate to a wild-type form of Salmonella, thus can never become pathogenic or harm anyone. Furthermore, Saltikva has been shown to preferentially invade and colonize within solid tumor tissues at a ratio of 1,000-10,000:1 over the normal ‘safe-sites’ of the liver. Saltikva carries the gene for a powerful anti-cancer immune stimulant, Interleukin-2, acting as an IL-2 factory once it has colonized the tumor tissue. It invades and colonize solid tumors after oral ingestion, releases a powerful immune stimulant directly within the tumor microenvironment thus avoiding systemic side effects, and imparts an NK-cell mediated anti-cancer response. Once in the tumor microenvironment, Saltikva also competes for nutrients therefore depriving the cancer cells.
Orally administered Saltikva has undergone extensive preclinical testing, a Phase 1 canine study, and a Phase 1 Clinical Human Trial. Recently, Saltikva was released on a compassionate basis to a patient with metastatic pancreatic cancer. With a median life expectancy of just 11 months, this patient is now in month 23 post-diagnosis and is feeling extremely well with complete resolution of her pulmonary metastases and significant diminution of her liver metastases and primary pancreatic cancer. A Phase II clinical study of Saltikva in metastatic pancreatic cancer is currently ongoing (NCT04589234).
Keywords: Saltikva, cancer, oncology, immune, therapy, immunotherapy, bacterial based cancer therapy, microbial immunotherapy, chemotherapy, pancreatic cancer, tumor microenvironment, immuno oncology, interleukin-2, cytokine, bacteria, Salspera