The therapeutic potency of Brother of the Regulator of Imprinted Sites (BORIS) against breast cancer suggests efficacy as a target antigen for a cancer vaccine, according to study results presented at the American Association for Cancer Research 101st Annual Meeting 2010.

A member of the cancer testis-antigen gene family, BORIS is an epigenetically-acting tumour-promoting transcription factor that is normally expressed in male germ cells, but can be activated in various malignancies, including breast cancer.

“BORIS is capable of inducing strong and effective antitumor immunity, but the efficacy of this immunotherapeutic strategy could be even better if one could eliminate immune suppressor cells, such as myeloid dervived suppressor cells and T regulatory cells,” said lead researcher 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.

Ample data indicate that the immune system could significantly inhibit cancer development and growth, leading to anticancer immunotherapy strategies in clinical settings. However, data also suggest that, to be effective, an antitumour vaccine should generate strong cellular immune responses to the target tumor-associated antigens.

Recent success in understanding the molecular biology of cancer provides new targets for immunotherapy of tumors, so called cancer-testis antigens.

Using a breast cancer mouse model, the researchers tested the immunotherapeutic potency of a mutated BORIS (mBORIS) vaccine delivered by dendritic cells. Dendritic cells are immune cells; they function as antigen-presenting cells that can bring target antigen to naïve T cells and induce cancer-specific cellular immunity.

"Recombinant mBORIS antigen delivered by dendritic cells into the body elicited strong antitumour cellular immune responses in tumor-free mice," said Agadjanyan. "More importantly, therapeutic vaccination dramatically inhibited both tumour growth and the number of metastases in the lungs of tumour-bearing mice."

Results showed that 18.75 percent of the mice remained tumor-free, while 50 percent remained metastases-free. Additionally, higher numbers of CD4- and CD8-positive T cells, which are responsible for antitumor immunity, infiltrated into the tumors of the vaccinated mice.

Levels of myeloid-derived suppressor cells and T regulatory cells detected in spleens isolated from vaccinated and control mice were similar, suggesting no change as a result of the vaccine. Importantly, these tumour-activated suppressor cells vigorously inhibited activation of CD4- and CD8-positive T cells.

"Although our data are encouraging, it is clear that even a vaccine based on a strong cancer-testis antigen, BORIS, does not completely inhibit tumor growth or eliminate metastatic disease in this model, which closely resembles human breast cancer," said Agadjanyan. "With increasing understanding of the interactions between the host immune system and tumors, traditional vaccines are inadequate for eliciting effective antitumor immune responses. Novel, multipronged approaches will be required. The BORIS-based vaccine or any other strong target antigen should be combined with strategies to limit the degree of tumor-associated immune suppression."