Vaccine With Promising Cancer-Fighting Abilities Developed

The results are published in the Jan. 20 issue of the Journal of the National Cancer Institute.

The team, led by Martin Sanda, M.D., assistant professor of urology surgery in the U-M Health System, constructed a genetically engineered vaccine containing a gene that elicited an immune response against a tumor challenge.

Mice given the vaccine, called vac-mTag, were found to have potent protection against a lethal mouse cancer caused by SV40.

Simian virus 40 became well-known in the late 1950's and early 1960's when it was discovered that polio vaccines given to nearly 100 million Americans were contaminated with SV40. To date, no study has found any direct evidence that SV40 causes cancer in humans.

SV40 produces T-antigen which was one of the first so-called oncogenes discovered. T-antigen is a large protein that causes tumors, and scientists first used it as a laboratory tool to alter normal cells, causing them to produce tumors. However, recent studies have found T-antigen in three rare, but extremely lethal human cancer types---mesothelioma (lung), osteosarcoma (bone) and ependymoma (brain). Researchers continue to study what role T-antigen actually plays in human tumor biology.

Sanda and his team constructed the vaccine by genetically removing the tumor-causing features from T-antigen, resulting in a protein that carries most of the parts that are recognized by the immune system.

"We made a vaccinia for the purpose of immunization that would cause the production of large amounts of T-antigen, lacking the parts that cause tumors while keeping the immune-activating portions intact," Sanda says. "Basically, we created a safety-modified T-antigen that could potentially be safe to use against the more dangerous full-length T-antigen in humans."

In the study, two groups of mice were vaccinated, one group with vac-mTag and the other with a control vector. Three weeks later, both groups were injected with tumor-causing cells. The group that received the vac-mTag showed a significantly potent immune response to the tumor challenge in both survival and tumor-free survival rates.

"The most significant aspect of our findings is that, using this new vaccinia construct, we can protect animals against T-antigen expressing tumors," Sanda says. Sanda says the next step is to prepare the vaccine for clinical applications. This entails

producing clinical-grade vac-mTag and performing FDA-mandated safety tests before launching a clinical trial for human patients. Sanda says he hopes to set up human trials on the vaccine in collaboration with investigators at Wayne State University in the next year or two.

Sanda says this study contributes to a larger effort. "Using a genetically engineered virus to stimulate the immune system against genetic abnormalities in tumors represents a paradigm with great future potential---that of applying information from cancer gene analysis to craft novel vaccines for cancer prevention.

"The usefulness of this particular vac-mTag vaccine may be greatest in the near future because development of human vaccines is now rigorously supervised to the point that it is unlikely humans will be exposed to SV40 in the future."

The study was performed in collaboration with the laboratory of Nicholas Restifo MD., at the National Cancer Institute and was funded by the National Institute of Health and the American Cancer Society.