Enhancement of anti-cancer immunity by a lipoteichoic-acid-related molecule isolated from a penicillin-killed group A Streptococcus.
We isolated the lipoteichoic-acid-related molecule (OK-PSA) from OK-432, a streptococcal preparation, by affinity chromatography on CNBr-activated Sepharose-4B-bound monoclonal antibody TS-2, which neutralizes the interferon (IFN)-gamma-inducing activity of OK-432. We have previously reported that OK-PSA is a potent inducer of Th1-type cytokines in human peripheral blood mononuclear cells in vitro. In this study, we conducted an animal experiment to examine whether OK-PSA exhibits an anti-tumor effect in vivo by acting as a Th1 inducer in syngeneic Meth-A tumor-bearing BALB/c mice, in which the Th2 response is genetically dominant. It was found that OK-PSA induced Th1-type cytokines [IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12 and IL-18] in BALB/c mice bearing Meth-A tumor and caused a marked anti-tumor effect. Although it was suggested by an in vitro study. using spleen cells derived from the animals, that IL-18 plays the greatest role in the induction of the Th1-dominant state and tumor cell killing induced by OK-PSA, the in vivo experiments demonstrated that both IL-12 and IL-18 are essential in the anti-tumor effect exhibited by OK-PSA. These findings strongly suggest that OK-PSA is a major effector molecule of OK-432 and may be a useful immunotherapeutic agent, as a potent Th1 inducer, for cancer patients with a Th2-dominant state.
Okamoto
M
M
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Japan.
Ohe
G
G
Oshikawa
T
T
Furuichi
S
S
Nishikawa
H
H
Tano
T
T
Ahmed
S U
SU
Yoshida
H
H
Moriya
Y
Y
Saito
M
M
Sato
M
M
D000276:Adjuvants, Immunologic / Q000302:isolation & purification / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D017209:Apoptosis; D002846:Chromatography, Affinity; D004354:Drug Screening Assays, Antitumor; D053222:Fas Ligand Protein; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000502:physiology; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008222:Lymphokines / Q000097:blood / Q000378:metabolism; D008223:Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy / Q000821:virology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008979:Moloney murine leukemia virus; D009368:Neoplasm Transplantation; D010400:Penicillin G / Q000494:pharmacology; D054353:Perforin; D010844:Picibanil / Q000737:chemistry; D052899:Pore Forming Cytotoxic Proteins; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013297:Streptococcus pyogenes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D013682:Teichoic Acids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D020382:Interleukin-18; D008070:Lipopolysaccharides; D008222:Lymphokines; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D054353:Perforin; D018664:Interleukin-12; D010844:Picibanil; C009900:lipoteichoic acid; D010400:Penicillin G