Concurrent Trastuzumab and HER2/neu-Specific Vaccination in Patients With Metastatic Breast Cancer

Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, WA 98195-8050, USa.
Journal of Clinical Oncology (Impact Factor: 18.43). 09/2009; 27(28):4685-92. DOI: 10.1200/JCO.2008.20.6789
Source: PubMed


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.
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.
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.
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.

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    • "Conversely, combination therapy with trastuzumab and an ErbB2/Neu T helper peptide vaccine was well tolerated and it was associated with minimal toxicity in patients with metastatic breast cancer. In addition, the combinatorial approach of the vaccine with passive immunotherapy resulted in prolonged, robust, antigen-specific immune responses in treated patients and induced epitope spreading [54]. In agreement with these evidences it is reasonable to investigate ErbB2 cancer vaccine approaches with the aim to improve the objective tumor inhibitory response in salivary gland carcinomas. "
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    • "This allows for specific tumor killing with minimal toxicity to surrounding normal tissue. This type of targeted immunotherapy is already being widely used in humans in the form of Her2/neu antibodies for breast cancer [6] [7] [8]. Antibody therapy is considered passive since its efficacy is based on a direct effect of the administered antibody on tumor cells and does not primarily depend on activation of the body's immune system. "
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    • "This expanded T-cell response is known as antigen spreading or antigen cascade,5 a process that can broaden and become more clinically relevant over time. In fact, emerging data show improved clinical outcomes in patients who mount a broad immunologic response.678 "
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