EFFECT OF IMMUNOMODULATORS ON SPECIFIC TUMOR-IMMUNITY INDUCED BY LIPOSOME-ENCAPSULATED TUMOR-ASSOCIATED ANTIGENS

Reconstituted membranes consist of liposomal structures formed by remo val of detergent from solubilized membrane constituents. The membrane- like configuration of reconstituted membranes makes them attractive as vehicles for presentation of tumor-associated antigens and induction of immune responses. In this study the potential of immunomodulators w as assessed to enhance the specific immune response induced by immuniz ation with reconstituted membranes prepared from SL2 lymphosarcoma cel ls. Reconstituted membranes containing muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) provided better protection against a challenge w ith SL2 cells than did reconstituted membranes containing alternative immunomodulators. Local administration of IL-2 at the immunization sit es further augmented the protection induced by reconstituted membranes with MTP-PE, but was ineffective when administered with plain reconst ituted membranes. Immunity elicited by the triple modality of reconsti tuted SL2 membranes with MTP-PE and IL-2 was specific for SL2 cells. S ystemic immunity was obtained against a challenge with a 100-fold high er number of SL2 cells than was reached after immunization with recons tituted membranes alone (10(5) vs. 10(3) SL2 cells). Macrophages isola ted from the peritoneal cavity of immunized mice 5 to 7 days after tum or challenge expressed high in vitro cytotoxicity. However, in contras t to the observed specificity of the systemic immunity, macrophages ki lled both SL2 cells and non-related P815 cells. Neither major cytotoxi c lymphocyte activity nor substantial cytotoxic antibody titers were d etectable. These results clearly indicate that the approach using reco nstituted membranes combined with particular immunomodulators warrants further exploration for the development of safe, well-characterized c ancer vaccines. (C) 1994 Wiley-Liss, Inc.