Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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MDP-Lys (L18), a Synthetic Muramyl Dipeptide Derivative, Enhances Antitumor Activity of an Inactivated Tumor Vaccine

  • Yoo, Yung-Choon (Department of Microbiology, College of Medicine, Konyang University) ;
  • Park, Seung-Yong (Department of Veterinary Medicine, Konkuk University) ;
  • Lee, Kyung-Bok (Department of Biochemistry, College of Medicine, Konyang University) ;
  • Azuma, Ichiro (Institute of Immunological Science, Hokkaido University, Hokkaido National College of Technology)
  • Published : 2000.06.01
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Abstract

The adjuvant effect of a muramyl dipeptide (MDP) derivative, MDP-Lys(L18), on enhancing of antitumor immunity induced by X-irradiated tumor cells against highly metastatic B16-BL6 melanoma cells was examined in mice. Mice immunized intradermally (i.d.) with a mixture of X-irradiated B16-BL6 cells and MDP-Lys (L18) [Vac+MDP-Lys (L18)] followed by an intravenous (i.v.)inoculation of $10^4$ viable tumor cells 7 days after immunization, showed a significant inhibition of experimental lung metastasis of B16-BL6 melanoma cells. The most effective immunization for the prophylactic inhibition of tumor metastasis was obtained from the mixture of $100{\;}\mu\textrm{g}$ of MDP-Lys (L18) and $10^4$ X-irradiatied tumor vaccine. Furthermore, immunization of mice with Vac+MDP-Lys(L18), 3 days after tumor challenge, resulted in a significant inhibition of lung metastasis of B16-BL6 melanoma cells in an experimental lung metastasis model. Similarly, the administration of Vac+MDP-Lys(L18), 1 or 7 days after tumor removal, markedly inhibited tumor metastasis of B16-BL6 in a spontaneous lung metastasis model. When Vac+MDP-Lys (L18) was i.d. administered 3 days after subcutaneous (s.c.) inoculation of tumor cells ($5{\times}10^5/site$) on the back, mice treated with Vac+MDP-Lys(L18) showed inhibition of significantly tumor growth on day 20. These results suggest that MDP-Lys (L18) is able to enhance antitumor activity induced by X-irradiated tumor vaccine to reduce lung metastasis of tumor cells, and is a potent immunomodulating agent which may be applied prophylactically as well as therapeutically to treatment of cancer metastasis.

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References

  1. Biochem. Biophys. Res. Commun. v.56 Adjuvant activity of monomeric bacterial cell wall peptidoglycans Adam, A.;R. Ciorbaru;F. Ellouz;J. F. Petit;E. Lederer
  2. Biochem. Biophys. Res. Commun v.72 Correlation of structure and adjuvant activity of N-acetylmuramyl-L-ananyl-D-isoglutamine(MDP), its derivatives and analogs. Antiadjuvant and competition properties of stereo-isomers Adam, A.;M. Devys;V. Souvannavong;P. Lefrancier;J. Choay;E. Lederer
  3. Arzneim.-Forsch./Drug Res. v.38 no.II Activation of immune responses by muroctasin Akasaki, M.
  4. Infect. Immun v.29 Adjuvant activity of N-acetyl muramyl dipeptides for the induction of delayed-type hypersensitivity to azobenzene-arsonate-N-acetyl-L-tyrosine in guinea pig Azuma, I.;K. Kamisango;I. Saiki;T. Tanio;S.Kobayashi;Y. Yamamura
  5. Vaccine v.10 Synthetic immunoadjuvants: Application to non-specific host stimulation and potentiation of vaccine immunogenicity Azuma, I.
  6. J. Reticuloendothel. v.26 Recent development concerning muramyldipeptide, a synthetic immunoregulating molecule Chedid, L.;L. Carelli;F. Audibert
  7. J. Med. Chem. v.25 Synthesis and immunoadjuvant activities of 2-acetamido-5-O-acetyl-6-O-acyl-2-deoxy-3-O-[(R)-2-propionyl-L-alanyl-D-isoglutamine]-D-glucofuranoses as potential prodrug forms of 6-O-Acyl derivatives of N-acetylmuramyl dipeptide Durette, P. L.;C. P. Jr. Don;A. Friedman;A. Schlabach
  8. Biophys. Res. Commun. v.59 Minimal structure requirement for adjuvant activity of bacterial peptidoglycan derivatives Ellouz, F.;A. Adam;R. Ciorbaru;E. Lederer
  9. J. Immunol. v.133 Synergism between lymphokine and muramyl dipeptide encapsulated in liposome: In situ activation of macrophage and therapy of spontaneous cancer metastasis Fidler, I. J.;A. J. Schroit
  10. Arzneim.-Forsch./Drug Res. v.39 Activation of the cytokine network by muroctasin as a remedy for leukopenia and thrombopenia Furuse, K.;A. Sakuma
  11. J. Microbiol. Biotechnol. v.9 Protective effects of Bifidobacterium spp. on experimental colon carcinogenesis with 1,2-dimethylhydrazine Han, M. J.;H. Y. Park;D. H. Kim
  12. Infect. Immun. v.46 Colony-stimulating activity induced by synthetic muramyl peptides: Variation with chemical structure and association with antiinfections activity Galelli, A.;P. Lefrancier;L. Chedid
  13. Vaccine v.7 Prophylactic activity against Sendai virus infection and macrophage activation with lipophilic derivatives of N-acetylglucosaminyl-muramyl tri-or tetrapeptides Iida, J.;I. Saiki;C. Ishihara;I. Azuma
  14. Vaccine v.5 Suppression of Sendai virus growth by treatment with $N^{α}-acetylmuramyl-_{L}-alanyl-_{D}-isoglutaminyl-N^{e}-stearoyl-_{L}-lysine in mice$ Ishihara, C.;N. Mizukoshi;J. Iida;K. Yamamoto;I. Azuma
  15. Vaccine v.7 Effect of $N^{α}-acetylmuramyl-_{L}-alanyl-_{D}-isoglutaminyl-N^{e}-stearoyl-_{L}-lysine on resistance to herpes simplex virus type-1 infection in cyclophosphamide-treated mice Ishihara, C.;J. Iida;N. Mizukoshi;N. Yamamoto;K. Yamamoto;K. Kato;I. Azuma
  16. Vaccine v.10 Use of low toxicity adjuvants and killed virus to induce protective immunity against the Friend murine leukemia retrobirus-induced disease Ishihara, C.;M. Miyazawa;J. Nishio;I. Azuma;B. Chesebro
  17. Vaccine v.10 Phase I clinical tests of influenza MDP-virosome vaccine (KD-5382) Kaji, M.;Y. Kaji;M. Kaji;T. Honda;T. Oka(et al.)
  18. J. Microbiol. Biotechnol. v.4 Immunostimulating effects of cell wall components isolated from Lactobacillus plantarum Kang, T. Y.;S. H. Park;T. B. Choe
  19. Science v.24 Human monocytes activated by immunomodulators in liposome lyse herpes virus infected but not normal cells Koff, W. C.;I. J. Fiedler;S. D. Showalter;M. K. Chakrabarty;B. Hampar;L. M. Ceccorulli;E. S. Kleinerman
  20. J. Immunol. v.136 Macrophage cytotoxicity: Interleukin 1 as a mediator of tumor cytostasis Lovett, D.;B. Kozan;M. Resch;D. Gemsa
  21. Microbial Immunol. v.25 Stimulation of nonspecific resistance to infection induced by muramyl dipeptides Matsumoto, K.;H. Ogawa;O. Nagase;T. Kusama;I. Azuma
  22. Infect. Immun. v.32 Stimulation of nonspecific resistance induced by 6-O-acyl muramyl dipeptide analogs in mice Matsumoto, K.;H. Ogawa;T. Kusama;O. Nagase;N. Sawaki;M. Inage;S. Kusumoto;T. Shiba;I. Azuma
  23. Infect. Immun v.39 Stimulation of nonspecific resistance to infection induced by muramyl dipeptide analogs substituted in the g-carboxy group and evaluation of $N^{α}-muramyl dipeptide-N^{e}-stearoyllysine$ Matsumoto, K.;T. Otani;T. Une;Y. Osada;H. Ogawa;I. Azuma
  24. Arzneim.-Forsch./Drug Res. v.38 no.II Stimulation of non-specific resistance to infection by muroctasin Otani, T.;T. Une;Y. Osada
  25. Immunobiology v.172 Human pluripotent hemopoietic colony stimulating factor: Activities on human and murine cell Platzer, E.;S. Oez;K. Welte;A. Sendler;J. L. Gabrilove;R. Mertelsmann;M. A. Moore;J. R. Kalden
  26. Vaccine v.6 Induction of tumoricidal macrophages and production of cytokines by synthetic muramyl dipeptide analogs Saiki, I.;S. Saito;C. Fujita;H. Ishida;J. Iida;J. Murata;A. Hasegawa;I. Azuma
  27. J. Exp. Med. v.159 Biological and antigenic similarities of murine interferon-γ and macrophage-activating factor Svedersky, L. P.;C. V. Benton;W. H. Berger;E. Rinderknecht;R. H. Harkins;M. A. Palladino
  28. Vaccine v.13 Effect of muramyl dipeptide derivatives as adjuvants on the induction of antibody response to recombinant hepatitis B surface antigen Tamura, M.;Y. C. Yoo;K. Yoshimatsu;R. Yoshida;T. Oka;K. Ohkuma;J. Arikawa;I. Azuma
  29. Arzneim.-Forsch./Drug Res. v.38 Restorative activity of muroctasin on leukopenia associated with anticancer treatment Tsubura, E.;T. Nomura;H. Niitani;T. Osamura;M. Tanaka;K. Ota(et al.)
  30. Infect. Immun v.53 Adjuvant activity of 6-O-acyl-muramyl dipeptides to enhance primary cellular and humoral immune responses in guinea pigs: Dose response and local reactions observed with selected compounds Tsujimoto;M.;S. Kotani;T. Shiba;S. Kusumoto
  31. Arzneim.-Forsch./Drug Res. v.38 Induction of colony-stimulating factor and stimulation of stem cell proliferation by injection of muroctasin Yamaguchi, F.;M. Akasaki;W. Tsukada
  32. Arzneim.-Forsch./Drug Res. v.38 Production of colony-stimulating factor from macrophages by muroctasin Yamaguchi, F.;K. Akahane;T. Takashi;W. Tsukada
  33. Vaccine v.10 B30-MDP, a synthetic derivative for tumour vaccination to enhance antitumour immunity and antimetastatic effect in mice Yoo, Y. C.;I. Saiki;K. Sato;I. Azuma
  34. Vaccine v.12 MDP-Lys(L18), a lipophilic dervative of muramyl dipeptide, inhibits the metastasis of haematogenous and non-haematogenous tumors in mice Yoo, Y. C.;I. Saiki;K. Sato;I. Azuma
  35. Vaccine v.13 Effect of MDP-Lys (L18), a derivative of MDP, on enhancing host resistance against Hantaan virus infection in newborn mice Yoo, Y. C.;K. Yoshimatsu;R. Hatsuse;M. Tamura;R. Yoshida;S. Tono-oka;J. Arikawa;I. Azuma
  36. Jpn. J. Cancer Res. v.88 Bovine lactoferrin and lactoferricin, a peptide ferived from bovine lactoferrin, inhibit tumor metastasis in mice Yoo, Y. C.;S. Watanabe;R. Watanabe;K. Hata;K. Shimazaki;I. Azuma
  37. Vaccine v.2/3 Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a hantavirus-inactivated vaccine Yoo, Y. C.;K. Yoshimatsu;Y. Koike;R. Hatsuse;K. Yamanishi;O. Tanishita;J. Arikawa;I. Azuma