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. 1985 Nov;28(5):589–596. doi: 10.1128/aac.28.5.589

Prevention of oncogenic viral infections in mice with CGP 11637, a synthetic muramyl dipeptide analog.

H F Acevedo, R B Raikow, H O Acevedo, T F Delgado, M Pardo
PMCID: PMC176340  PMID: 3867329

Abstract

The efficacy of N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine (nor-MDP) in controlling viral oncogenesis in mice was investigated. The tumors studied were blood cell malignancies induced by Friend leukemia virus in SJL/J mice, spontaneous mammary neoplasms in RIII/Imr and C3H/OuJ mice, and spontaneous lymphocytic leukemia in AKR/J mice. A transplantable tumor, Lewis lung carcinoma, in C57BL/6J mice was used as a nonvirally induced control model. The nor-MDP was dissolved in saline and made into an emulsion with an equal volume of squalene-Arlacel A and injected subcutaneously at 1- to 2-month intervals. Test and control mice were challenged with exogenous virus or tumor transplant 2 weeks after a second injection of nor-MDP. Administration was started at around 2 months of age in mice that develop spontaneous neoplasms. Electron microscopy studies were done on neoplastic tissues of selected test and control mice. This administration of nor-MDP prevented erythroleukemia in SJL/J mice caused by low doses of Friend leukemia virus (although erythroleukemia survivors were not protected from a late-developing lymphoma) and also delayed (possibly prevented) the development of a spontaneous mammary neoplasm in RIII/Imr mice. No antitumor effects were observed on the spontaneous neoplasms of C3H/OuJ and AKR/J mice or on the Lewis lung carcinoma implanted into C57BL/6J mice. Electron microscopic examinations of the various neoplastic tissues indicated that nor-MDP administration eliminated or reduced extracellular viruses. The results suggested that under the experimental conditions used nor-MDP appears to effect the viruses and not the malignant cells per se.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnon R., Sela M., Parant M., Chedid L. Antiviral response elicited by a completely synthetic antigen with built-in adjuvanticity. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6769–6772. doi: 10.1073/pnas.77.11.6769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. CHIRIGOS M. A., LUBER E., MARCH R., PETTIGREW H. ANTIVIRAL CHEMOTHERAPEUTIC ASSAY WITH FRIEND LEUKEMIA VIRUS IN MICE. Cancer Chemother Rep. 1965 Apr;45:29–33. [PubMed] [Google Scholar]
  3. Chedid L. A., Parant M. A., Audibert F. M., Riveau G. J., Parant F. J., Lederer E., Choay J. P., Lefrancier P. L. Biological activity of a new synthetic muramyl peptide adjuvant devoid of pyrogenicity. Infect Immun. 1982 Feb;35(2):417–424. doi: 10.1128/iai.35.2.417-424.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chedid L., Carelli C., Audibert F. Recent developments concerning muramyl dipeptide, a synthetic immunoregulating molecule. J Reticuloendothel Soc. 1979 Dec;26(Suppl):631–641. [PubMed] [Google Scholar]
  5. Durette P. L., Dorn C. P., Jr, Friedman A., Schlabach A. 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. J Med Chem. 1982 Sep;25(9):1028–1033. doi: 10.1021/jm00351a005. [DOI] [PubMed] [Google Scholar]
  6. Fidler I. J., Poste G. Activation of tumoricidal properties in murine macrophages by intravenous injection of muramyl dipeptide encapsulated within liposomes as a treatment for spontaneous metastasis. Prog Clin Biol Res. 1981;75B:257–267. [PubMed] [Google Scholar]
  7. Fraser-Smith E. B., Eppstein D. A., Larsen M. A., Matthews T. R. Protective effect of a muramyl dipeptide analog encapsulated in or mixed with liposomes against Candida albicans infection. Infect Immun. 1983 Jan;39(1):172–178. doi: 10.1128/iai.39.1.172-178.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. GROSS L. Pathogenic properties, and "vertical" transmission of the mouse leukemia agent. Proc Soc Exp Biol Med. 1951 Oct;78(1):342–348. doi: 10.3181/00379727-78-19068. [DOI] [PubMed] [Google Scholar]
  9. Hays E. F., Vredevoe D. L. A discrepancy in XC and oncogenicity assays for murine leukemia virus in AKR mice. Cancer Res. 1977 Mar;37(3):726–730. [PubMed] [Google Scholar]
  10. Kireszenbaum F., Ferraresi R. W. Enhancement of host resistance against Trypanosoma cruzi infection by the immunoregulatory agent muramyl dipeptide. Infect Immun. 1979 Jul;25(1):273–278. doi: 10.1128/iai.25.1.273-278.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Koff W. C., Showalter S. D., Hampar B., Fidler I. J. Protection of mice against fatal herpes simplex type 2 infection by liposomes containing muramyl tripeptide. Science. 1985 Apr 26;228(4698):495–497. doi: 10.1126/science.2984772. [DOI] [PubMed] [Google Scholar]
  12. Krahenbuhl J. L., Sharma S. D., Ferraresi R. W., Remington J. S. Effects of muramyl dipeptide treatment on resistance to infection with Toxoplasma gondii in mice. Infect Immun. 1981 Feb;31(2):716–722. doi: 10.1128/iai.31.2.716-722.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kumar R. K. Hodgkin's disease. SJL/J murine lymphoma. Am J Pathol. 1983 Mar;110(3):393–396. [PMC free article] [PubMed] [Google Scholar]
  14. Lederer E. Synthetic immunostimulants derived from the bacterial cell wall. J Med Chem. 1980 Aug;23(8):819–825. doi: 10.1021/jm00182a001. [DOI] [PubMed] [Google Scholar]
  15. McLaughlin C. A., Schwartzman S. M., Horner B. L., Jones G. H., Moffatt J. G., Nestor J. J., Jr, Tegg D. Regression of tumors in guinea pigs after treatment with synthetic muramyl dipeptides and trehalose dimycolate. Science. 1980 Apr 25;208(4442):415–416. doi: 10.1126/science.7189295. [DOI] [PubMed] [Google Scholar]
  16. Moore D. H., Holben J. A. Effect of parity regimen on the rate of occurrence of mammary tumors in A, C3H, and RIII mice. Int J Cancer. 1979 Aug;24(2):161–164. doi: 10.1002/ijc.2910240206. [DOI] [PubMed] [Google Scholar]
  17. Osada Y., Mitsuyama M., Une T., Matsumoto K., Otani T., Satoh M., Ogawa H., Nomoto K. Effect of L18-MDP(Ala), a synthetic derivative of muramyl dipeptide, on nonspecific resistance of mice to microbial infections. Infect Immun. 1982 Jul;37(1):292–300. doi: 10.1128/iai.37.1.292-300.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Polk H. C., Jr, Calhoun J. H., Lowrey L. D., Blanchard S. P., Brewer R. J., Adams S. T., Chedid L. Nonspecific enhancement of host defenses against infection: experimental evidence of a new order of efficacy and safety. Surgery. 1981 Aug;90(2):376–380. [PubMed] [Google Scholar]
  19. Polk H. C., Jr, Galland R. B., Ausobsky J. R. Nonspecific enhancement of resistance to bacterial infection: evidence of an effect supplemental to antibiotics. Ann Surg. 1982 Oct;196(4):436–441. doi: 10.1097/00000658-198210000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Raikow R. B., Meredith R. F., Brozovich B. J., Seeman P. R., Livingston A. E., Okunewick J. P. Potentiating effect of methyl methane sulfonate on Friend virus leukemogenesis in vivo. Proc Soc Exp Biol Med. 1979 Jun;161(2):210–215. doi: 10.3181/00379727-161-40522. [DOI] [PubMed] [Google Scholar]
  21. Rose W. C., Bortin M. M., Saltzstein E. C. Prolonged survival of AKR mice following allogeneic bone marrow transplantation. Experientia. 1974 Sep 15;30(9):1085–1086. doi: 10.1007/BF01939025. [DOI] [PubMed] [Google Scholar]
  22. Rouben D. P., Fagelman K., McCoy M. T., Polk H. C., Jr Enhancement of nonspecific host defenses against local bacterial challenge. Surg Forum. 1977;28:44–45. [PubMed] [Google Scholar]
  23. SIEGLER R., RICH M. A. UNILATERAL HISTOGENESIS OF AKR THYMIC LYMPHOMA. Cancer Res. 1963 Nov;23:1669–1678. [PubMed] [Google Scholar]
  24. Schroit A. J., Fidler I. J. Effects of liposome structure and lipid composition on the activation of the tumoricidal properties of macrophages by liposomes containing muramyl dipeptide. Cancer Res. 1982 Jan;42(1):161–167. [PubMed] [Google Scholar]
  25. Sone S., Tachibana K., Shono M., Ogushi F., Tsubura E. Potential value of liposomes containing muramyl dipeptide for augmenting the tumoricidal activity of human alveolar macrophages. J Biol Response Mod. 1984;3(2):185–194. [PubMed] [Google Scholar]
  26. Sone S., Tsubura E. Human alveolar macrophages: potentiation of their tumoricidal activity by liposome-encapsulated muramyl dipeptide. J Immunol. 1982 Sep;129(3):1313–1317. [PubMed] [Google Scholar]
  27. Sugimoto M., Germain R. N., Chedid L., Benacerraf B. Enhancement of carrier-specific helper T cell function by the synthetic adjuvant, N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP). J Immunol. 1978 Mar;120(3):980–982. [PubMed] [Google Scholar]
  28. Tanaka A., Emori K. Epithelioid granuloma formation by a synthetic bacterial cell wall component, muramyl dipeptide (MDP). Am J Pathol. 1980 Mar;98(3):733–748. [PMC free article] [PubMed] [Google Scholar]
  29. Waters R. V., Ferraresi R. W. Muramyl dipeptide stimulation of particle clearance in several animal species. J Reticuloendothel Soc. 1980 Nov;28(5):457–471. [PubMed] [Google Scholar]

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