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In Mice, Combining Cancer Vaccine and Low-Dose Anti-Angiogenesis Drug Shows Promise against Breast Cancer

A combination of a therapeutic cancer vaccine and low doses of a drug that blocks tumor blood vessel growth (an angiogenesis inhibitor) may be an effective treatment for breast cancer, according to a study in mice.

In two different mouse models of breast cancer, the combination treatment shrank tumors more than either treatment alone, and in one model it also improved survival. Dr. Rakesh Jain and his colleagues from Massachusetts General Hospital and Harvard Medical School published the findings October 8 in the Proceedings of the National Academy of Sciences.

Evidence from both human and animal studies has suggested that lower doses of angiogenesis inhibitors can "normalize" tumor blood vessels, making them less leaky and more functional-an effect that could improve the delivery of other therapies. And several recent studies suggest that abnormal tumor vasculature "fosters an immunosuppressive [tumor] microenvironment" that may help tumors evade detection or attack by the immune system, the researchers wrote. If so, they continued, normalizing the vasculature could improve vaccine efficacy.

They tested low and high doses of the angiogenesis inhibitor DC101 alone or in combination with a therapeutic vaccine in different mouse models of breast cancer. Based on previous research, they explained, "the schedule of combination treatment…was designed to synchronize vascular normalization and T-cell activation [by the vaccine]." The researchers also looked for clues that could explain why the combination of the vaccine and low-dose angiogenesis inhibitor was more effective. Compared with blood vessels in mice that received higher doses of DC101 and the vaccine, they found that those in mice treated with lower doses of DC101 and the vaccine were more stable and more evenly distributed throughout the tumor. This appeared to increase the infiltration of immune cells into the tumor following vaccination and to encourage a stronger immune response to the tumor.

According to Dr. James Gulley of NCI's Center for Cancer Research (CCR), the study findings are consistent with recent research conducted by Dr. Benedetto Farsaci in CCR's Laboratory of Tumor Immunology and Biology, involving a therapeutic cancer vaccine in combination with sunitinib (Sutent).

Clinical trials to test a therapeutic vaccine with low doses of an angiogenesis inhibitor in women with breast cancer are in the early planning stages, Dr. Jain said.

Source: NCI Cancer Bulletin http://www.cancer.gov/ncicancerbulletin/103012/page3#d
PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/23045683