VESICLES FOR TUMOR-ASSOCIATED ANTIGEN PRESENTATION TO INDUCE PROTECTIVE IMMUNITY - PREPARATION, CHARACTERIZATION AND ENHANCEMENT OF THE IMMUNE-RESPONSE BY IMMUNOMODULATORS

Tumour-associated antigens (TAA) that are expressed on tumour cells ca n induce resistance to tumour transplants in immunized syngeneic hosts . In this report three issues related to tumour vaccines are discussed . (1) Solubilization of TAA from tumour cells and their presentation o n a membrane-like structure to the immune system. Proteins and lipids were solubilized from crude membranes of SL2 lymphosarcoma cells with octylglucoside (OG). By removal of OG from the OG-lipid-protein micell es, vesicles (0.13 mu m) consisting of cell membrane constituents were formed. These vesicles were used to immunize DBA/2 mice against a cha llenge with syngeneic SL2 cells. Specific, protective tumour immunity was observed. (2) The tumour rejection potential of these vesicles was stimulated by addition of the immunomodulators muramyl tripeptide pho sphatidylethanolamine (MTP-PE) and/or interleukin-2 (IL-2). Moreover, the effect of liposome encapsulation of IL-2 on its immunomodulating e ffect was investigated. (3) Attention was paid to physically and chemi cally characterize the formulations to improve reproducibility of the antitumour effect. Finally, the loading capacity of liposomes for the cytokine IL-2 was optimized by increasing the electrostatic interactio n between the liposomal bilayer and IL-2.