PROTECTION OF MICE AGAINST SV40 TUMORS BY PAM(3)CYS, MTP-PE AND PAM(3)CYS CONJUGATED WITH THE SV40-T ANTIGEN-DERIVED PEPTIDE, K(698)-T(708)

The intraperitoneal injection of Balb/c mice with synthetic analogues of adjuvants almitoyloxy)-(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 synge neic simian virus 40 (SV40)-transformed cell line. Furthermore, the Pa m(3)Cys conjugate of K698-T708 (KT), which represents the C-terminal u ndecapeptide of the SV40 large tumour (T) antigen was tumour-protectiv e. 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 w as impaired by treatment of the mice with either anti-CD4, anti-CD8 Ig G, anti asialo GM1 antiserum or dextrane sulfate, which deplete the CD 4(+), CD8(+) and NK cells or the macrophages, respectively. In summary , SV40 tumour transplantation resistance can be experimentally elicite d by a tumour-epitope-specific vaccina. In the absence of an immunogen ic epitope protection was obtained by administration of biological res ponse modifiers. Protection is effected by SV40-T-antigen-specific cyt otoxic lymphocytes in cooperation with NK cells and macrophages. (C) 1 997 Elsevier Science Ltd. All lights reserved.