The overall goal of this program is to utilize immunologic, molecular, and synthetic approaches to develop means for treating AIDS and controlling HIV infection. The specific approaches to be employed include: 1) generation of HIV specific cytolytic T lymphocyte clones and investigation of the potential for using such clones in adoptive cellular immunotherapy, 2) detailed studies of the interactions between viral envelope glycoprotein and CD4 determinants critically involved in the pathobiology of HIV infection, using synthetic peptide and recombinant DNA approaches to identify and develop therapeutic agents capable of interrupting these crucial interactions between the viral envelope and CD4, 3) production and functional characterization of mouse/human chimeric antibodies and immunotoxin conjugates for selective targeting and destruction of infected cells expressing HIV antigens, and 4) generation of HIV- derived vectors and a viral packaging line for selective targeting and expression of defined genetic sequences to effect blockade of HIV replication and/or removal of HIV infected cells from the host. This multidisciplinary approach involves scientists at three institutions and takes advantage of the special areas of expertise of the Program Leaders and of technical resources already well established in our laboratories, and is based on extensive ongoing collaborative interactions between the Program Leaders. In addition, the research program outlined in this proposal incorporates approaches directed against several distinct phases of the viral life cycle with the ultimate goal of developing a synergistic, multimodal approach of the type that will probably be ultimately required for effective therapy of HIV infection.
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