Monday, April 19, 2010
A new study in mice suggests that a novel antigen discovered in NIAID’s Laboratory of Immunopathology (LIP) could be effective as a target for an antitumor vaccine, according to a presentation delivered at the 101st annual meeting of the American Association for Cancer Research.
The antigen, called Brother of the Regulator of Imprinted Sites (BORIS), was discovered and characterized in 2001 by LIP scientists Victor V. Lobanenkov, Ph.D.; Dmitri I. Loukinov, Ph.D.; and Herbert C. Morse III, M.D. It is a tumor-promoting protein that normally is expressed in developing male reproductive cells, but frequently can be activated in various malignancies. Previous studies have shown that the immune system can inhibit cancer development and growth, and researchers are evaluating the potential role of cancer-testis antigens such as BORIS as targets for immunotherapies against tumors.
To facilitate the delivery of BORIS to the immune system, NIAID scientists combined a mutated version of the protein with dendritic cells, immune cells which present foreign substances to naïve T cells and thereby induce antigen-specific cellular immunity. Researchers led by Michael G. Agadjanyan, Ph.D., D.Sc., head of the department of immunology and professor at the Institute for Molecular Medicine and adjunct professor at the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, then tested the mutated BORIS/dendritic cell vaccine in a mouse model of highly aggressive breast cancer.
Dr. Agadjanyan’s team found that the vaccine both inhibited tumor growth and lowered the number of metastases (tumors spreading to other parts of the body). In their experiments, nearly one-fifth of the vaccinated mice remained tumor-free, and half of the vaccinated mice remained free of metastases. In addition, higher numbers of CD4- and CD8-positive T cells infiltrated the tumors of vaccinated mice than those of the unvaccinated control mice. CD4-positive cells help initiate the immune response against an antigen, while CD8-positive cells specialize in destroying infected, cancerous, or otherwise damaged cells.
The team’s analysis also showed that the tumors that grew despite vaccination could still suppress other elements of the immune system that would help fight tumors. Finding ways to limit this tumor-associated immune suppression will be an important next step toward further development of this strategy as a potential cancer vaccine.
M Mkrtichyan et al. A novel cancer-testis antigen, BORIS-based vaccine delivered by dendritic cells is effective against metastatic disease. Abstract LB-319. Presented during the 101st Annual Meeting of the American Association for Cancer Research; Apr 17-21, 2010; Washington, DC.
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Last Updated April 16, 2010
Last Reviewed April 16, 2010