Carson Iii WE, Kaumaya PT. Combined vaccination with HER-2 peptide followed by therapy with VEGF peptide mimics exerts effective anti-tumor and anti-angiogenic effects in vitro and in vivo

The Ohio State University
OncoImmunology (Impact Factor: 6.27). 10/2012; 1(7):1048-1060. DOI: 10.4161/onci.20708
Source: PubMed


Overexpression of HER-2 and VEGF plays a key role in the development and metastasis of several human cancers. Many FDA-approved therapies targeting both HER-2 (Trastuzumab, Herceptin) and VEGF (Bevacizumab, Avastin) are expensive, have unacceptable toxicities and are often associated with the development of resistance. Here, we evaluate the dual antitumor effects of combining designed particular HER-2 peptide vaccine with VEGF peptide mimics. In vitro, HER-2 phosphorylation and antibody-dependent cellular toxicity were used to validate whether combining HER-2- and VEGF-targeting therapies would be effective. Moreover, a two-pronged approach was tested in vivo: (1) active immunotherapy with conformational HER-2 B-cell epitope vaccines and (2) anti-angiogenic therapy with a peptide structured to mimic VEGF. A transplantable BALB/c mouse model challenged with TUBO cells was used to test the effects of the HER-2 peptide vaccine combined with VEGF peptide mimics. Tumor sections after treatment were stained for blood vessel density and actively dividing cells. Our results show that immunization with an HER-2 peptide epitope elicits high affinity HER-2 native antibodies that are effective in inhibiting tumor growth in vivo, an effect that is enhanced by VEGF peptide mimics. We demonstrate that the combination of HER-2 and VEGF peptides induces potent anti-tumor and anti-angiogenic responses.

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Available from: Pravin T Kaumaya
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    • "Studies from our laboratory have shown that a combined approach produces superior antitumor effects in vitro and in vivo when compared to single treatments (Foy et al., 2011). Immunization with our novel HER2 epitope vaccine, followed by VEGFR peptide mimic treatment, increased survival and significantly delayed tumor growth in mouse models of cancer (Foy et al., 2012b). We also evaluated a multi-modality approach in which low doses of chemotherapy (paclitaxel) combined with HER2 or VEGF peptide mimics improved response outcomes and minimized toxicity (Foy et al., 2012a). "
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