Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic
 

<dl class="AbstractPlusReport"><dt class="head">1: J Clin Oncol. 2009 Oct 1;27(28):4685-92. Epub 2009 Aug 31.http://www.ncbi.nlm.nih.gov/corehtml...d-jco_full.gif <script language="JavaScript1.2"><!-- var Menu19720923 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=1972 0923&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubm ed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubme d_RVAbstractPlus' ", "", ""] ] --></script>Links
</dt><dd class="abstract"> Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer.

<!--AuthorList-->Disis ML, Wallace DR, Gooley TA, Dang Y, Slota M, Lu H, Coveler AL, Childs JS, Higgins DM, Fintak PA, dela Rosa C, Tietje K, Link J, Waisman J, Salazar LG.
Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, WA 98195-8050, USa. ndisis@u.washington.edu
PURPOSE: The primary objectives of this phase I/II study were to evaluate the safety and immunogenicity of combination therapy consisting of concurrent trastuzumab and human epidermal growth factor receptor 2 (HER2)/neu-specific vaccination in patients with HER2/neu-overexpressing metastatic breast cancer. PATIENTS AND METHODS: Twenty-two patients with stage IV HER2/neu-positive breast cancer receiving trastuzumab therapy were vaccinated with an HER2/neu T-helper peptide-based vaccine. Toxicity was graded according to National Cancer Institute criteria, and antigen specific T-cell immunity was assessed by interferon gamma enzyme-linked immunosorbent spot assay. Data on progression-free and overall survival were collected. RESULTS: Concurrent trastuzumab and HER2/neu vaccinations were well tolerated, with 15% of patients experiencing an asymptomatic decline in left ventricular ejection fraction below the normal range during combination therapy. Although many patients had pre-existing immunity specific for HER2/neu and other breast cancer antigens while treated with trastuzumab alone, that immunity could be significantly boosted and maintained with vaccination. Epitope spreading within HER2/neu and to additional tumor-related proteins was stimulated by immunization, and the magnitude of the T-cell response generated was significantly inversely correlated with serum transforming growth factor beta levels. At a median follow-up of 36 months from the first vaccine, the median overall survival in the study population has not been reached. CONCLUSION: Combination therapy with trastuzumab and a HER2/neu vaccine is associated with minimal toxicity and results in prolonged, robust, antigen-specific immune responses in treated patients.
PMID: 19720923 [PubMed - in process]
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