This proposal seeks to join the efforts of two laboratory and clinical programs to investigate biologic characteristics of HIV NHL and develop novel therapeutics. Using existing agents based on previous studies of NHL, a pilot clinical trial is proposed using an anti-B cell immunoconjugate. This study is a model for future clinical trials using biological agents and is the point of initiation for correlative laboratory studies to better understand the pathophysiology of HIV NHL. The laboratory studies focus on defining the regulation of HIV NHL B cell proliferation and that structures which determine the localization of these cells. These features have been selected for study because of their apparent connection with the clinically observed phenomena of polyclonal proliferation of B cells prior to the emergence of a malignant clone and the proclivity of the tumor for extranodal sites of disease. In addition, these phenomena may lend themselves to the development of therapeutic agents due to their involvement of cell surface structures potentially accessible to cytokine or adhesion based therapeutics.
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