A Chimeric Multi-Human Epidermal Growth Factor Receptor-2 B Cell Epitope Peptide Vaccine Mediates Superior Antitumor Responses

摘要: Immunotherapeutic approaches to cancer should focus on novel undertakings that modulate immune responses by synergistic enhancement of antitumor immunological parameters. Cancer vaccines preferably be composed multiple defined tumor Ag-specific B and T cell epitopes. To develop a multiepitope vaccine, 12 high ranking epitopes were identified from the extracellular domain human epidermal growth factor receptor-2 (HER-2) oncoprotein computer-aided analysis. Four HER-2 synthesized as chimeras with promiscuous epitope (aa 288–302) measles virus fusion protein (MVF). Two chimeric peptide vaccines, MVF 316–339 485–503 induced levels Abs in outbred rabbits, which inhibited growth. In addition, combination two 628–647 down-modulated receptor expression activated IFN-γ release better than individual vaccines. Furthermore, this vaccine IL-12 caused significant reduction ( p = 0.004) number pulmonary metastases challenge syngeneic cells overexpressing HER-2. Peptide targeting specific sites may used for exploring oncoprotein’s functions. The have potential application treatment HER-2-associated cancers.