MANY IMMUNOSTIMULATORY AGENTS ARE AVAILABLE WHICH ARE POTENTIAL MACROPHAGE ACTIVATING AGENTS.

MANY IMMUNOSTIMULATORY AGENTS ARE AVAILABLE WHICH ARE POTENTIAL MACROPHAGE ACTIVATING AGENTS. HOWEVER, THEIR IN VIVO ABILITY TO INDUCE ANTITUMOR ACTIVITY IN MACROPHAGE IS SEVERELY LIMITED DUE TO THE RAPID CLEARANCE OF THESE AGENTS. THIS PROJECT PROPOSES TO USE PHOSPHOLIPID VESICLES (LIPOSOMES) AS A DELIVERY SYSTEM FOR MACROPHAGE ACTIVATING FACTORS. THE LIPOSOME DELIVERY SYSTEM WILL ENHANCE THE EFFICACY OF THESE AGENTS BY EXTENDING THEIR TIME IN CIRCULATION AND BY INCREASING THE AMOUNT OF AGENT DELIVERED TO MACROPHAGE. PHASE I WILL DEMONSTRATE A LIPOSOME FORMULATION WHICH SATISFIES THE OBJECTIVES OF PROLONGED BIOLOGICAL LIFETIMES FOR THE ACTIVATING AGENTS AND INCREASED DELIVERY TO BLOOD MONOCYTES AND PULMONARY AND HEPATIC MACROPHAGE. PHASE II WILL DETERMINE THE THERAPEUTIC EFFICACY OF THE DELIVERY SYSTEM USING LIPOSOME-ENCAPSULATED MACROPHAGE ACTIVATING FACTORS IN VIVO IN TUMOR-BEARING MICE AND IN VITRO IN CULTURES OF HUMAN MONOCYTES. SUCCESSFUL COMPLETION OF PHASES I AND II WILL PROVIDE THE NECESSARY PRECLINICAL DATA TO SUPPORT TRIALS OF A NEW CLASS OF THERAPEUTIC AGENTS FOR TREATING SEVERAL HUMAN CANCERS.