Alpha Omega Alpha Honor Medical Society

2012 Research Abstract

Determining whether HER-2 pulsed DC1 vaccines in DCIS patients induce humoral or cellular immune responses that prevent breast cancer invasion

Investigator: Megan Fracol, Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania

Mentor: Brian J. Czerniecki, MD, PhD, Harrington Rhoads Professor of Surgical Oncology, Program Director Penn Breast Fellowship, Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania

Nearly one in eight women will develop breast cancer in their lifetime. Of those, breast neoplasms over-expressing human epidermal growth factor receptor-2 (HER-2) have a higher distant metastasis rate and a poorer prognosis. As the immune system plays a pivotal role in surveilling for and preventing tumor cell growth, recent interest in targeted cancer therapeutics have turned towards vaccine development to activate the immune system against tumor associated antigens, with the goal of decreasing tumor burden and preventing recurrence. Our group has designed a HER-2 pulsed autologous dendritic cell (DC1) vaccine that has been shown to elicit cellular and humoral immune responses against HER-2 peptide and protein as well as elicit tumor regression in ductal carcinoma in situ (DCIS). Given the complex interplay of signaling molecules in vivo, we sought to determine in an in vitro model of breast cancer invasion whether patient post-vaccination serum could block breast cancer invasion. We first identified that anti- HER-2 and anti-HER-3 antibodies could inhibit invasion of the breast cancer cell line MDA-MB-231. Additionally, four of ten patient serum post-vaccination samples were able to block invasion from 40-70%. All four patients developed CD4 T cells that reacted against HER-2 and/or HER-3. Our results suggest that DC1 vaccines can induce antibodies post-vaccination at least in some patients that can prevent or block invasion of breast cancer and offers opportunities to develop preventive vaccines against HER- family members that may halt progression of breast cancer.

Updated on February 6, 2013.

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