HER-2/neu Cancer Vaccines: Present Status and Future Prospects |
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Authors: | Pravin T P Kaumaya |
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Institution: | (1) Departments of Obstetrics and Gynecology (Division of Reproductive Biology and Vaccine Research), Molecular and Cellular Biochemistry, Microbiology, Molecular Virology, Immunology and Medical Genetics, and the Arthur G. James Cancer Hospital and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA;(2) 316 Tzagournis Medical Research Facility, 420 W12th Avenue, Columbus, OH 43210, USA |
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Abstract: | Immunotherapeutic approaches to cancer should focus on novel undertakings that modulate immune responses by synergistic enhancement
of anti-tumor immunological parameters. Cancer vaccines should preferably be composed of multiple defined tumor antigen specific
B- and T-cell epitopes. The main focus of this article is to briefly review the present status of Her-2/neu vaccine strategies
and to describe the innovative strategies developed in my laboratory for a vaccine against HER-2/neu (ErbB-2) with emphasis
on the humoral arm of the immune response. Elucidating the underlining mechanisms of anti-tumor effects elicited by peptide
vaccines against a self-protein is a requirement for developing an immunotherapeutic strategy that might be effective in human
cancer vaccines. Our approach entails the identification of biologically relevant epitopes, establishing relevant in vitro assays for monitoring vaccine efficacy, devising strategies to engineer conformationally dependent sequences, developing
highly immunogenic vaccines for an outbred population and delivering the immunogen/vaccine in a safe and efficacious vehicle,
utilizing transgenic animal models for assessing tumor development, and developing challenge models using transplantable tumors
to study efficacy of vaccine constructs. We have developed a multi-HER-2/neu B-cell epitope approach and shown in preclinical
studies that immunization with a combination of two B-cell epitope was more effective in preventing mammary tumors than a
single epitope. We have translated that work to the clinic (OSU 0105) in an FDA approved, NCI sponsored “Phase 1 Active Immunotherapy trial with Chimeric and Multi-epitope based peptide vaccine targeting HER-2 oncoprotein and
nor-MDP adjuvant in patients with metastatic and/or recurrent solid tumors” at the James Cancer Hospital at the Ohio State University. The correlation between overexpression of HER-2/neu and up-regulation of VEGF has been demonstrated in breast cancer patients. Thus, blocking angiogenesis is an attractive strategy
to inhibit tumor growth, invasion, and metastasis. The hypothesis that combination of anti-angiogenic therapy and tumor immunotherapy
of cancer may be synergistic is an important future goal. In this review, I will discuss insights into our preclinical studies
that might aid in the design of the next generation of cancer vaccines and become an integrated component of prophylactic/preventive
and therapeutic approach. |
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Keywords: | Tumor therapy multi-epitopes chimeric peptide vaccines her-2 b-cell epitopes |
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