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 (Pam3Cys) 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 Pam3Cys 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 Pam3Cys-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 vaccine. 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.
Obert
M
M
Abteilung Virologie, Universität Freiburg, Germany.
Pleuger
H
H
Hanagarth
H G
HG
Schulte-Mönting
J
J
Wiesmüller
K H
KH
Braun
D G
DG
Brandner
G
G
Hess
R D
RD
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000008:administration & dosage* / Q000276:immunology; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D005260:Female; D007114:Immunization; D007155:Immunologic Factors / Q000008:administration & dosage*; D008074:Lipoproteins / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000008:administration & dosage* / Q000276:immunology; D030361:Papillomavirus Infections / Q000517:prevention & control*; D010714:Phosphatidylethanolamines / Q000008:administration & dosage* / Q000276:immunology; D013539:Simian virus 40 / Q000276:immunology*; D014412:Tumor Virus Infections / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D000957:Antigens, Viral, Tumor; D007155:Immunologic Factors; C089279:K698-T708 undecapeptide; D008074:Lipoproteins; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C069172:2,3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine; D003545:Cysteine