Protection of mice against SV40 tumours by Pam3Cys, MTP-PE and Pam3Cys conjugated with the SV40 T antigen-derived peptide, K(698)-T(708)

The intraperitoneal injection of Balb/c mice with synthetic analogues of adjuvants S-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-R-cysteine (Pam(3)Cys) or muramyltripeptide phosphatidylethanolamine (MTP-PE) inhibited the tumourigenic growth of subcutaneously injected VLM cells, a syngeneic simian virus 40 (SV40)-transformed cell line. Furthermore, the Pam(3)Cys conjugate of K698-T708 (KT), which represents the C-terminal undecapeptide of the SV40 large tumour (T) antigen was tumour-protective. Also syngeneic spleen cells, preincubated in vitro with this Pam(3)Cys-KT derivative, which anchores spontaneously at the cell membrane, were, through SV40 tumour mimicry, tumour-protective. The protection was impaired by treatment of the mice with either anti-CD4, anti-CD8 IgG, anti asialo GM1 antiserum or dextrane sulfate, which deplete the CD4(+), CD8(+) and NK cells or the macrophages, respectively. In summary, SV40 tumour transplantation resistance can be experimentally elicited by a tumour-epitope-specific vaccina. In the absence of an immunogenic epitope protection was obtained by administration of biological response modifiers. Protection is effected by SV40-T-antigen-specific cytotoxic lymphocytes in cooperation with NK cells and macrophages. (C) 1997 Elsevier Science Ltd. All lights reserved.