A research team at Mayo Clinic in Rochester, Minn., has used the immune systems of mice to eradicate cancerous tumors in a genetic combination of human DNA from melanoma cells delivered directly into tumors through the highly immunogenic vector vesicular stomatitis virus (VSV). In early studies, 60 percent of tumor-burdened mice were cured in less than three months and with minimal adverse effects.
In this cancer immunotherapy-based technology, successful tumor eradication is associated with the ability of mouse lymphoid cells to mount a tumor-specific CD4+ interleukin-17 recall response in vitro. The research team used this characteristic response to screen the VSV-complementary DNA (cDNA) library and identified three different VSV-cDNA virus clones that, when used in combination but not alone, were as effective in inducing tumor rejection as the complete parental virus library in mice with melanoma.
The research team will use this technology to define repertoires of tumor-associated antigens that work in combination to induce antitumor immune responses for other cancers. The identification of arrays of tumor-associated antigens that cooperate in vivo to cure established tumors may also permit the cloning of antigens that can play a role in the development of cancer vaccines. Jose S. Pulido, M.D., an ocular oncologist at Mayo Clinic in Minnesota, is a coauthor of the study, which was published in Nature Biotechnology in April 2012.
For more information
Pulido JS, et al. Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma. Nature Biotechnology. 2012;30:337.
Points to remember
- Cancer immunotherapy strategy uses a genetically engineered version of VSV to deliver a broad spectrum of genes derived from melanoma cancer cells directly into tumors.
- Researchers will use this technology to identify combinations of antigens that work to induce anti-tumor responses for other cancers.
- The identification of arrays of antigens that cooperate to eradicate established tumors will also inform strategies for the development of clinical vaccines.
- A cDNA library is a combination of cloned cDNA fragments inserted into a collection of host cells that together constitute some portion of the set of all RNA molecules produced in one cell or a population of cells of the organism.