TARGET TO SPECIFIC LYMPHOID CELLS. PHASE I. MACROPHAGE TARGETING.

A THREE PHASE PROJECT IS PROPOSED TO COMMERCIALIZE FORMULATIONS OF PHOSPHOLIPID VESICLES CAPABLE OF DELIVERING IMMUNOGENIC SUBSTANCES TO SPECIFIC LYMPHOID CELLS. PHASE I IS A PROOF OF CONCEPT STUDY DESIGNED TO DEMONSTRATE THAT A VESICLE FORMULATION KNOWN TO AGGRESSIVELY TARGET TO MACROPHAGE IN VITRO CAN EVOKE STRONG MACROPHAGE MEDIATED IMMUNE RESPONSES TO OTHERWISE WEAK OR NONIMMUNOGENIC HAPTEN CONJUGATES IN VIVO. PHASE I EXPERIMENTS SPECIFICALLY ADDRESS THE MACROPHAGE MEDIATED B-CELL RESPONSE AND ARE DESIGNED TO DETERMINE THE SIGNIFICANCE OF THE SIZE OF THE HAPTEN CARRIER WHEN TARGETED WITH VESICLES. PHASE I SHOULD SUGGEST ANSWERS TO THE FOLLOWING QUESTIONS: 1) IS AN ENDOCYTOSED VESICLE PROCESSED AS AN IMMUNOGEN BEFORE OR AFTER LYSIS BY MACROPHAGE? 2) ARE LYSOZOME LABILE CARRIERS PROCESSED AS ANTIGENS OR DEGRADED WHEN ENDOCYTOSED WITHIN TARGETED VESICLES? 3) ARE HAPTEN-CONJUGATES, TARGETED TO MACROPHAGE BY VESICLE ENCAPSULATION, IMMUNOGENIC AT LOWER DOSAGES THAN CONVENTIONALLY INTRODUCED HAPTEN-CONJUGATES? SUCCESSFUL COMPLETION OF PHASE I WILL DEMONSTRATE THAT IMMUNE RESPONSE CAN BE ALTERED BY PRESENTING CHEMICAL SUBSTANCES TO SPECIFIC CELLS IN A MICROENCAPSULATED FORMULATION. PHASE II WILL EXTEND THIS PRELIMINARY INVES- TIGATION OF DELIVERING HAPTEN-CONJUGATE FORMULATIONS TO MACROPHAGE TO INCORPORATE HELPER T-CELL PARTICIPATION IN THEINITIAL ANTICIPATED T-CELL INDEPENDENT RESPONSE. THE PRODUCTION OF IMMUNE RESPONSES TO WEAKLY IMMUNOGENIC OR NON-IMMUNOGENIC MATERIALS HAS SIGNIFICANT SCIENTIFIC AND MEDICALAPPLICATIONS.