Peptide-mediated immunotherapy of KSHV-associated malignancy Research Area: 5-DE-109 Novel Immunotherapies to Treat HIV/AIDS-related Oral Manifestations and AIDS Malignancies Kaposi sarcoma (KS), specifically oral KS, is the leading cause of cancer in patients with HIV infection. While there is a reduction in the incidence of oral KS among patients receiving HAART, an increasing concern is the development and spread of drug resistant HIV-1 strains, which in turn leads to reoccurrence of oral complication. Kaposi's sarcoma-associated herpesvirus (KSHV) is an etiological agent to induce KS tumors, pleural effusion lymphomas and multicentric Castleman's disease. We have recently developed a new primate model that significantly recapitulates the important aspects of the KSHV infection and pathogenesis of humans, thus providing a unique tool for the development of potential therapeutic strategies against KSHV infection. Autophagy is a new, emerging cellular pathway in which dynamic morphological changes of subcellular membranes leads to the degradation of proteins and organelles. This process also plays a role in the anti-microbial and anti-tumor responses of the host by degrading intracellular microbes and by suppressing cancer cell growth, respectively. We discover the autophagy death- inducing therapeutic activity of the viral FLIP short peptides. Thus, the goal of this proposal is to test the efficacy of the vFLIP peptide as a therapeutic agent against KSHV-associated malignancies in culture and xenografted murine model (Approach1) and in common marmoset primate model (Approach 2). PUBLIC HEALTH RELEVANCE: Kaposi sarcoma (KS), specifically oral KS, is the leading cause of cancer in patients with HIV infection. The goal of this proposal is to test the efficacy of the vFLIP peptide as a therapeutic agent against KSHV-associated malignancies in culture and xenografted murine model and in common marmoset primate model.