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  • Title: Protein vaccination with the HER2/neu extracellular domain plus anti-HER2/neu antibody-cytokine fusion proteins induces a protective anti-HER2/neu immune response in mice.
    Author: Dela Cruz JS, Lau SY, Ramirez EM, De Giovanni C, Forni G, Morrison SL, Penichet ML.
    Journal: Vaccine; 2003 Mar 28; 21(13-14):1317-26. PubMed ID: 12615426.
    Abstract:
    Previously protein vaccines consisting of the extracellular domain of HER2/neu (ECD(HER2)) were shown to elicit an immune response that does not provide protection against transplantable tumors expressing HER2/neu. Here, we showed that when mice were vaccinated with a mixture of human ECD(HER2) and anti-human HER2/neu IL-12, IL-2 or GM-CSF fusion proteins, significant retardation of the growth of a syngeneic carcinoma expressing rat HER2/neu, and long-term survivors were observed. Immune sera inhibited the in vitro growth of SK-BR-3, a human breast cancer overexpressing HER2/neu. Transfer of immune sera into mice challenged with TUBO also led to partial inhibition of tumor growth. Splenocytes from mice vaccinated with ECD(HER2) plus IgG3-(GM-CSF) incubated with ECD(HER2) demonstrated significant proliferation and IFN-gamma secretion. Taken together these results suggest that vaccines including ECD(HER2) and Ab-cytokine fusion proteins may be used to elicit both humoral and cell-mediated responses against HER2/neu.
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