Vaccination with cetuximab mimotopes and biological properties of induced anti-epidermal growth factor receptor antibodies.

摘要: Background: The monoclonal antibody cetuximab (IMC-225, Erbitux) inhibits epidermal growth factor receptor (EGFR) signaling and has been approved for metastatic colon cancer therapy. However, to achieve effective titers, passive therapies must be repeatedly administered over long periods. To overcome this limitation, we aimed generate a vaccine inducing continuously available “ cetuximab-like ” antibodies in vivo using the mimotope approach. Methods: We used phage display technique identify four peptides structurally mimicking epitope. coupled two of these an immunogenic carrier protein, vaccinated groups (n = 8) BALB/c mice intraperitoneally with 10 μ g conjugates, control peptide conjugate, or protein alone. assessed antibodydependent cellular cytotoxicity complement-dependent mediated by induced against EGFR-overexpressing human A431 carcinoma cells. then tested internalization capacity fl uorescently labeled EGFR, assayed their inhibitory potential toward cells [ 3 H]thymidine proliferation assay. Results: Mimotope-induced recognized both types antibodymediated cytotoxic effects were elicited antibodies. In assays, mimotope-induced exhibited specifi c lysis more than 50%. caused from cell surface into endocytic vesicles inhibited EGFR-expressing similar extent as [67% (95% confi dence interval {CI} 55% 79%) 69% CI 84%), respectively]. Conclusions: Epitopespecifi immunization is feasible active anti-EGFR immunotherapy. vitro biologic features mimotopeinduced are those cetuximab. [J Natl Cancer Inst 2005;97:1663 – 70]