The purpose is to understand the biology and immunology of laryngeal papillomtosis and to explore the possibility of a new approach to the treatment of this disease. We hope to develop better ways to prevent, control or cure laryngeal papillomas. Specific studies to be done can be grouped into two broad groups. In Project 1, cultured laryngeal epithelial cells will be microinjected with HPV DNA to study the early events in HPV infection and to determine the effect of viral copy number on those events. Project 4 will use HPV DNA transfection of epidermal keratinocytes as a model to study latent papilloma virus infection. These two projects complement each other, and the results from each will aid in the interpretation of the other in furthering or understanding of the mechanism of HPV infection and transformation in laryngeal papillomas. The studies described in Project 3 are also concerned directly with the cell biology of HPV infected epithelial cells. This project proposes to continue to prepare monoclonal antibodies against papilloma-associated proteins, and to use these antibodies to study the role of HPV induced or HPV coded regulatory proteins in the transformation to a benign papilloma. Project 2 and 5 are concerned with the treatment of papilloma patients and the functioning of the immune system in these patients, respectively. Project 2 will explore a possible new therapy for laryngeal papillomas, using Hematoporphyrin derivative and laser exposure. This therapy will first be tested on cutaneous rabbit papillomas. Project 5 will analyze the immunme status of the patients and the ability of their NK and T cells to recognize specific virally infected target cells. This study should detect subtle immunodysfunction in the laryngeal papilloma patients.
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