Phase I Clinical Trial with Her-2 B-Cell Chimeric and MultiEpitope Based Peptide Vaccines in Patients with Metastatic and/or Recurrent Solid Tumors

摘要

Trastuzumab and Pertuzumab are two humanized Abs that target two different regions of the extracellular domain of HER-2/neu. Although humanized Mabs have been approved by the FDA, a number of concerns still exist. They are expensive and require repeated administration due to their limited duration of action and produce side effects like cardiotoxicity. We have evaluated the safety, toxicity and immunogenicity of increasing doses of two chimeric HER-2 B-cell epitope vaccines derived from the extracellular domain (ECD) in patients with metastatic and or recurrent solid tumors. Twenty four patients received three inoculations at the intended dose levels and the vaccine was well tolerated, with the maximum tolerable dose (MTD) being the highest dose level (1.5mg each of MVF-316-339 and MVF 628-647) (Table 1) [1] as no dose limiting toxicity was identified for any dose level. After vaccination, four patients were judged to stable disease, two patients had partial response and eleven patients had progressive disease. Anti-peptide abs recognized HER-2 and inhibited HER-2/neu -specific cellular proliferation and receptor phosphorylation. The antibodies were also able to cause antibody dependent cellular cytotoxicity (ADCC) of HER-2 positive cells. This study shows the safety and immunogenicity of the vaccine in a population of patients with metastatic disease.