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Endocrine and Oncologic Surgery Research Lab
Harrison Department of Surgical Research
Brian J. Czerniecki, M.D., Ph.D.
 
Development of Dendritic Cell Vaccines
for Breast Cancer Prevention
 
We have become one of the leading groups in the development of dendritic cell (DC) for the treatment of early breast cancer ductal carcinoma in situ (DCIS). Since DCIS and invasive breast cancer (IBC) share very similar risk factors, developing successful immune based therapies for DCIS can be translated into treatments for IBC and can be used to develop prevention strategies for breast cancer. We conducted a phase I trial treating HER-2/neu positive DCIS patients in a neoadjuvant setting with DC vaccines. We selected HER-2/neu as a target antigen because HER-2/neu expressing DCIS is associated with greater risk of recurrence, and as pointed out below we have noted an association between HER-2/neu expression and the progression to invasive breast cancer. Recently HER-2/neu expression has also been shown to be expressed in some breast cancer stem cells. For these reasons we hypothesized that targeting HER-2/neu in early breast cancer could be useful for developing vaccines for treatment of DCIS, IBC, and develop for breast cancer prevention. Preliminary results were published in Czerniecki et. al Cancer Research 67:1842-52, 2007 and Cancer Res. 67:6531-4 2007. Briefly we documented that that these vaccines induce immune responses in about 90% of patients and induce significant loss of HER-2/neu with over 50% of patients having complete loss of target HER-2/neu and 18% of patients demonstrating no evidence of DCIS remaining in the breast following vaccination. A manuscript describing the final results of the trial is about to be submitted for publication. In addition, we have documented for the first time that a HER-2/neu vaccine can induce asymptomatic declines in cardiac function and there is a need to monitor patients’ cardiac function with effective vaccines similar to treatment with trastuzumab Bahl et. al American Journal of Surgery (In Press). These studies were funded by the NIH and renewed this past December 2008, to continue a clinical trial to assess whether we could completely eradicate disease by conditioning both the local and systemic immune response using these HER-2/neu pulsed DC vaccines. This trial was recently opened and is accruing patients.
 

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