Associate Professor, Department of Microbiology & Immunology
New approaches to develop vaccines against metastatic breast cancer
Breast cancer is the most common cancer among women around the world, and 40% of the women diagnosed with breast cancer will progress to metastatic disease. Current treatment is not effective against metastases. However, cancer patients mostly die from metastases and not from primary tumors. Recently, our laboratory has developed DNA-based cancer vaccines that are effective against metastases. The long-term goal of our research is to further improve cancer vaccination for application in human clinical trials. To reach this goal, various approaches are under investigation.
Listeria-based cancer vaccines
We have developed vaccines, encoding tumor-specific antigens using an attenuated non-toxic and non-pathogenic bacterium Listeria monocytogenes (LM). LM delivers tumor-specific antigens with high efficiency directly into antigen presenting cells, resulting in activation of tumor-specific cytotoxic T lymphocytes (CTL) that subsequently kill tumor cells.
Most tumors produce factors that inhibit vaccine-induced T cell responses in vivo. One such factor is interleukin (IL)-6. Currently, we are investigating combination therapies of Listeria-Mage-b vaccine and Curcumin. Curcumin is a non-toxic Indian spice that down regulates IL-6.
The importance of the age factor in cancer vaccination
More than 50% of all cancer patients are 65 years or older. However, vaccines are less effective at older age than young age, due to T cell unresponsiveness. Our laboratory found that adaptive anti-tumor immune responses (CTL) are strongly reduced, but innate immune responses (macrophages and natural killer cells) are still active at old age. Therefore, we are modifying our vaccines using alternative approaches, i.e., vaccines that activate innate immune responses and induce apoptotic pathways in tumor cells at older age.
Most recent publications
Gravekamp C, Leal B, Denny A, Bahar R, Lampkin S, Castro F, Moore D, and Reddick R. In vivo responses to vaccination with Mage-b, GM-CSF and thioglycollate in a highly metastatic mouse breast tumor model, 4T1. Cancer Immunology and Immunotherapy 57: 1067-1077, 2008.
Kim SH, Castro F, Gonzalez D, Maciag P, Paterson Y, and Gravekamp C. Mage-b delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases. British Journal of Cancer 99: 741-749, 2008
Gravekamp C, Kim SH, and Castro F. Cancer vaccination: manipulation of immune responses at old age. Mechanisms of Ageing and Development. 2008. (In Press). DOI: 10.1016/j.mad.2008.05.003.
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