Generation of Peptide mimics of the epitope recognized by trastuzumab on the oncogenic protein Her-2/neu.

摘要: Immunizations with the oncogenic protein Her-2/neu elicit Abs exerting diverse biological effects--depending on epitope specificity, tumor growth may be inhibited or enhanced. Trastuzumab (herceptin) is a growth-inhibitory humanized monoclonal anti-Her-2/neu Ab, currently used for passive immunotherapy in treatment of breast cancer. However, Ab therapies are expensive and have to repeatedly administered long periods time. In contrast, active immunizations produce ongoing immune responses. Therefore, study aims generate peptide mimics recognized by trastuzumab vaccine formulation, ensuring subsequent induction inhibitory Abs. We phage display technique mimics, mimotopes, complementing screening trastuzumab. Five candidate mimotopes were isolated from constrained 10 mer library. These peptides specifically trastuzumab, showed distinctive mimicry two experimental setups. Subsequently, immunogenicity selected mimotope was examined BALB/c mice. synthetic conjugated tetanus toxoid resulted recognizing blotted cell lysate as well SK-BR-3 surface. Analogous induced caused internalization receptor surface endosomal vesicles. results indicate that suitable formulation cancer because resulting show similar features