Assessing the Immunogenicity of pING-hHER3FL

The human epidermal growth factor receptor (HER) family including HER1 (also known as EGFR), HER2, HER3 and HER4 (also known as ErbB2, ErbB3, and ErbB4 respectively) is an important receptor family for the development of many malignancies. HER3 is overexpressed in breast, lung, gastric, head and neck, and ovarian cancer and melanoma and its overexpression is associated with poor prognosis. Because of the negligible tyrosine kinase function of HER3, it is typically present in heterodimers with HER1 or HER2, through which downstream signaling occurs involving extracellular-signal-regulated kinase (ERK) 1/2 and AKT. In breast cancer, HER3 is associated with resistance to anti-HER2 therapeutics. HER3 is also one of several important causes of endocrine resistance in breast cancer. A HER3 specific cancer vaccine that induces polyclonal antibody and T cell responses can provide long term anti-HER3 immune responses and potentially prevent the emergence of resistant clones. In addition to the long term protection afforded by vaccination, polyclonal immune responses to a target protein may offer additional benefits. It has been established that the binding of multiple antibodies to different epitopes is more efficient than a single monoclonal antibody in mediating receptor internalization. Additionally, T cell responses induced by vaccination are also a potent mechanism of tumor rejection in numerous animal studies and the adoptive transfer of T cells in human clinical trials has shown clinical efficacy. Although HER3 is expressed on a number of normal tissues, and is only rarely mutated in cancers, it remains an attractive immunotherapeutic target as it is not abundant on the cell surface in normal cells, tumor cells may have higher levels of membrane-bound HER3, and HER3 peptides are presented on the cell surface by MHC complexes for presentation to T cells. The primary objective of the study is to evaluate the safety of immunization with pING-hHER3 in patients with solid tumor malignancies that have been removed surgically. The study will also monitor immune responses to HER3 and preliminary data on survival and tumor response rate will be collected.