Enhancement of anti-cancer immunity by a lipoteichoic-acid-related molecule isolated from a penicillin-killed group A Streptococcus

Autor: Tomoyuki Tano, Hidetomo Nishikawa, Masato Okamoto, Yoichiro Moriya, Sachiko Furuichi, Motoo Saito, Tetsuya Oshikawa, Go Ohe, Mitsunobu Sato, Sharif Uddin Ahmed, Hideo Yoshida
Rok vydání: 2001
Předmět:
Lipopolysaccharides
Cancer Research
Lymphoma
Fibrosarcoma
medicine.medical_treatment
Apoptosis
Chromatography
Affinity
Picibanil
Mice
Interferon
Tumor Cells
Cultured
Immunology and Allergy
Inducer
Lymphokines
Mice
Inbred BALB C
Membrane Glycoproteins
Interleukin-18
Antibodies
Monoclonal
Interleukin
Penicillin G
Interleukin-12
Killer Cells
Natural
Cytokine
Oncology
Female
Tumor necrosis factor alpha
Lipoteichoic acid
medicine.drug
Pore Forming Cytotoxic Proteins
Fas Ligand Protein
Streptococcus pyogenes
Immunology
Antineoplastic Agents
Biology
Peripheral blood mononuclear cell
Th2 Cells
Adjuvants
Immunologic
In vivo
medicine
Animals
fas Receptor
Perforin
Tumor Necrosis Factor-alpha
Th1 Cells
Molecular biology
Teichoic Acids
Drug Screening Assays
Antitumor
Moloney murine leukemia virus
Neoplasm Transplantation
Spleen
Zdroj: Cancer Immunology, Immunotherapy. 50:408-416
ISSN: 1432-0851
0340-7004
DOI: 10.1007/s002620100207
Popis: 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.
Databáze: OpenAIRE
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