ANTIBODY HETEROCONJUGATES FOR TREATMENT OF SIV INFECTION

THE GOAL OF THIS PROJECT IS TO GENERATE AND CHARACTERIZE A BISPECIFIC HETEROCONJUGATE ANTIBODY CAPABLE OF INDUCING THE CYTOLYSIS OF SIV-INFECTED CELLS. THE APPROACH IN PHASE I STUDY WILL ENTAIL CONJUGATING AN ANTI-CD3 MONOCLONAL ANTIBODY WITH AN ANTIBODY SPECIFIC FOR RECOMBINANT SIV ENVELOPE GLYCOPROTEIN GPL40. THE CYTOTOXIC ACTIVITY WILL BE TESTED IN AN IN VITRO SYSTEM USING CELLS INFECTED WITH RECOMBINANT VACCINIA VIRUS WHICH EXPRESS THE SIV ENV GENE AS TARGETS AND A HUMAN CTL LINE AS EFFECTORS. PHASE II STUDY WILL INVOLVE TESTING THE HETEROCONJUGATE IN VITRO AGAINST SIV-INFECTED CELLS USING CTL FROM SIV-INFECTED MACAQUES AS EFFECTORS. IN ADDITION, THE ABILITY OF THE ANTI-SIV HETEROCONJUGATE TO SUPPRESS VIRUS AND PREVENT DISEASE IN INFECTED MACAQUES WILL BE ASSESSED. THE DEVELOPMENT AND IN VIVO TESTING OF THE ANTI-SIV HETEROCONJUGATE WOULD PROVIDE AN EXCELLENT MEANS OF EVALUATING THIS TYPE ON IMMUNOTHERAPY FOR THE CLINICAL TREATMENT OF HIV-INFECTED HUMANS.