Isoprinosine and NPT 15392: Immunomodulation and Cancer

  • L. N. Simon
  • F. K. Hoehler
  • D. T. McKenzie
  • J. W. Hadden
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 166)

Abstract

In cancer, there appears to be a direct relationship between immunosuppression and the ability of neoplastic cells to flourish. Because the immune system is compromised, tumor growth is unchecked by the normal immune regulatory mechanisms. For this reason it has been suggested that immunomodulators, agents that directly affect immune function, might be used therapeutically in the treatment of cancer. Such compounds could restore the body’s capacity to mount an immunologic response leading to the eventual destruction of the neoplasm. Perhaps better supported by clinical evidence, is the possible use of immunomodulators as adjuvants to standard cancer therapies, such as chemotherapy or radiotherapy. The generalized immunosuppression resulting from these procedures often leads to severe problems with opportunistic infections. Used in combination with standard chemotherapy or radiotherapy, immunomodulators might speed the recovery of normal immune function thereby not only reducing the incidence of recurrence but also reducing the likelihood of infection. Immunomodulators, therefore, might be used either as a primary cancer therapy or as an adjuvant to established therapies. In this paper we review recent investigations which support the potential application of two immunomodulators, Isoprinosine and NPT 15392, in cancer therapy.

Keywords

Natural Killer Activity Human Peripheral Blood Lymphocyte Ehrlich Ascitic Tumor Mixed Lymphocyte Culture Pokeweed Mitogen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Reference

  1. 1.
    Ballet, J. J., A. M. Morin and M. Agrapart. 1980. Modulation by Isoprinosine of the activation, differentiation and antigen specific responses of human lymphocytes in vitro. 4th Congress of Immunology, Paris, France.Google Scholar
  2. 2.
    Betts, R. F., R. G. Douglas, Jr., S. D. George and C. J. Rinehart. 1978. Isoprinosine in experimental influenza Ainfection in volunteers. 78th Annual Meeting of the American Society for Microbiology, Las Vegas, Nevada.Google Scholar
  3. 3.
    Bradshaw, L. J. and H. L. Sumner. 1977. In vitro studies on cell-mediated immunity in patients treated with inosiplex for herpes virus infection. Ann. N.Y. Acad. Sci. 284: 190–196.PubMedCrossRefGoogle Scholar
  4. 4.
    Corey, L., W. Chiang, W. Reeves, W. Stamm, L. Brewer and K. Holmes. 1979. Effect of Isoprinosine on the cellular immune response in initial genital herpes virus infection. Clin. Res 27: 41A.Google Scholar
  5. 5.
    Deodhar, S. Unpublished observations.Google Scholar
  6. 6.
    Fenton, J., 1981. Etude en double-insu de l’influence de l’isoprinosine sur les tests immunitaire de patients recevant une irradiation pelvienne. Bull. Cancer. 68: 200.Google Scholar
  7. 7.
    Florentin, I., L. Kraus, G. Mathe and J. W. Hadden. 1982. In vivo study in mice of the immunopharmacological properties of NPT 15392. In B. Serrou et al (eds.), Proceedings of the international meeting on human cancer immunology. Elsevier- North Holland (in press).Google Scholar
  8. 8.
    Florentin, I., E. Taylor, M. Davigny, G. Mathe and J. W. Hadden. 1982. Kinetic studies of the immunopharmacologic effects of NPT 15392 in mice. Int. J. Immunopharm. 4: 225–234.CrossRefGoogle Scholar
  9. 9.
    Fridman, H., R. Calle and A. Morin. 1980. Double-blind study of Isoprinosine influence on immune parameters in solid tumor-bearing patients treated by radiotherapy. Int. J. Immunopharm. 2:: 194.Google Scholar
  10. 10.
    Goutner, A. 1980. In vitro modulation of natural killer cell activity by Isoprinosine, NPT 15392 and interferon. -Int. J. Immunopharm. 2: 197.Google Scholar
  11. 11.
    Hadden, J. W. and A. Giner-Sorolla. 1981. Isoprinosine and NPT 15392: modulators of lymphocyte and macrophage development and function. In E. M. Hersh et al (eds.), Augmenting agents in cancer therapy. Raven Press, New York.Google Scholar
  12. 12.
    Hadden, J. W. and T. Ginsberg. 1982. Immunopharmacology of methisoprinol. International symposium on recent advances in immunomodulators. Viarregio, Italy.Google Scholar
  13. 13.
    Hadden, J. W., E. M. Hadden and R. G. Coffey. 1976. Isoprinosine augmentation of phytohemagglutinin-induced lymphocyte proliferation. Infect. Immun. 13: 382–387.PubMedGoogle Scholar
  14. 14.
    Hadden, J. W., E. M. Hadden and R. G. Coffey. 1979. Biological significance of the purine salvage pathway. Transplant. Clin. Immunol. 10: 143–153.Google Scholar
  15. 15.
    Hadden, J. W., E. M. Hadden, T. Spira, R. Settineri, L. Simon and A. Giner-Sorolla. 1982. Effects of NPT 15392 in vitro on human leukocyte functions. Int. J. Immunopharm. 4: 235–242.CrossRefGoogle Scholar
  16. 16.
    Hadden, J. W., C. Lopez, R. O’Reilly and E. Hadden. 1977. Levamisole and inosiplex: antiviral agents with immunopotentiating action. Ann. N. Y. Acad. Sci. 284: 139–152.PubMedCrossRefGoogle Scholar
  17. 17.
    Hadden, J. W. and J. Wybran. 1981. Immunopotentiators II Isoprinosine, NPT 15392 and Azimexone: modulators of lymphocyte and macrophage development and function. In J. Hadden et al (eds.), Advances in immunopharmacology. Pergamon Press, New York.Google Scholar
  18. 18.
    Ikehara, S., J. W. Hadden, R. A. Good, D. G. Lunzer and R. N. Pahawa. 1981. In vitro effects of two immunopotentiators, Isoprinosine and NPT 15392, on murine T-cell differentiation and function. Thymus 3: 87–95.PubMedGoogle Scholar
  19. 19.
    Jones, E. C., B. Binko, R. Settineri and K. Maxwell. 1982. Influence of NPT 15392 on mouse and human lymphocyte responses (in preparation).Google Scholar
  20. 20.
    Kott, E., N. Gadoth, S. Levin, T. Hahn, V. Bergman, R. Avidor and C. Braun. 1981. Stimulation of the interferon system by Isoprinosine (inosiplex) in subacute sclerosing panencephalitis (SSPE). 13th Symposium of Israeli Immunological Society.Google Scholar
  21. 21.
    Merluzzi, V. J., M. M. Walker, N. Williams, B. Susskind, J. W. Hadden and R. B. Faanes. 1982. Immunoenhancing activity of NPT 15392: a potential immune response modifier. Int. J. Immunopharm. 4: 219–224.CrossRefGoogle Scholar
  22. 22.
    Micksche, M., E. M. Kokoschka, H. Rainer and A. Uchida. 1982. Augmentation of natural killer (NK) cell activity in cancer patients by NPT 15392. Int. J. Immunopharm. 4: 283.CrossRefGoogle Scholar
  23. 23.
    Morin, A., J. L. Touraine, G. Renoux and J. W. Hadden. 1980. Isoprinosine as an immunomodulating agent. Symposium of New Trends in Human Immunology and Cancer Immunotherapy, Montpellier, France.Google Scholar
  24. 24.
    Moulias, R., J. Proust, M. Marescot, M. Piette and A. Devulecharbrolle. 1978. Action of Isoprinosine (inosiplex) on the immunological parameters of aged people. 7th International Congress of Pharmacology. Paris, France.Google Scholar
  25. 25.
    Sato, S. and M. Tsurufuji. 1980. NPT 15392: immunorestorative effects in tumor-suppressed mice. Int. J. Immunopharm. 2: 200.CrossRefGoogle Scholar
  26. 26.
    Sato, S. Unpublished observations.Google Scholar
  27. 27.
    Schaison, G., E. Gluckman, J. F. Souilllet and J. M. Turc. 1980. Isoprinosine curative and prophylactic treatment of viral infections in patients with malignant hematologic disorders. 4th International Congress of Immunology. Paris, France.Google Scholar
  28. 28.
    Simon, L. N., A. Giner-Sorolla and J. W. Hadden. 1980. NPT 15392 a novel immunomodulating agent. 4th International Congress of Immunology. Paris, France.Google Scholar
  29. 29.
    Simon, L. N. and A. J. Glasky. 1978. Isoprinosine: an overview. Cancer Treatment Report. 62: 1963–1969.Google Scholar
  30. 30.
    Simon, L. N., R. Settineri, E. P Pfadenhauer, C. Jones, K. Maxwell and A. J. Glasky. 1980. NPT 15392: a pharmacologic and toxicologic profile. Int. J. Immunopharm. 2: 200.CrossRefGoogle Scholar
  31. 31.
    Talpaz, M. and G. Mavligit. 1982. Immune restoration augmentation by Isoprinosine in cancer patients. 2nd International Conference of Immunopharmacology. Washington, D. C.Google Scholar
  32. 32.
    Touraine, J. L., J. W. Hadden and F. Touraine. 1979. Isoprinosine-induced T-cell differentiation and T-cell suppressor activity in humans. 19th International Conference on Antimicrobial Agents and Chemotherapy., Boston, Mass.Google Scholar
  33. 33.
    Touraine, J., G. Gay-Ferret, K. Sanadji, 0. Othmane, G. Fournie and F. Touraine. 1982. Syngergistic effect with NPT 15392 in vitro and activity on suppressor T-lymphocytes in autoimmune mice in vivo. Internal Symposium on New Trends in Human Immunology and Cancer Immunotherapy. Montpellier, France.Google Scholar
  34. 34.
    Tsang, K. Y., C. B. Phillips, M. J. Gnagy and H. H. Fudenberg. 1982. In vivo and in vitro effects of NPT 15392 on the immune responses of hamsters. Fed. Proc. 41: 812.Google Scholar
  35. 35.
    Tsang, K. Y., M. J. Gnagy, C. B. Phillips and H. H. Fudenberg. 1981. In vitro effects of Isoprinosine (Iso) on the immune responses of cancer patients. Proceedings 13th International Cancer Congress. Seattle, Washington.Google Scholar
  36. 36.
    Wybran, J. 1978. Inosiplex, a stimulating agent for normal human T-cells and human leukocytes. J. Immunology. 121: 1184–1187.Google Scholar
  37. 37.
    Wybran, J. 1981. Immunomodulatory properties of Isoprinosine in man: in vitro and in vivo data. International Symposium on New Trends in Human Immunology and Cancer Iumtunotherapy. Montpellier, France.Google Scholar
  38. 38.
    Wybran, J. 1980. NPT 15392, a new synthetic immunomodulatory agent: human, in vitro and in vivo (cancer patients) effects. Int. J. Immunopharm. 2: 193.Google Scholar
  39. 39.
    Wybran, J. 1982. Immunomodulatory properties of NPT 15392 in man: in vitro and in vivo. Int. J. Immunopharm. 4: 292.Google Scholar
  40. 40.
    Wybran, J., J. P. Famaey, R. Gortz, I. Dab, A. Malfroot and T. Appelboom. 1982. Inosiplex (Isoprinosine): a review of its immunological and clinical effects in disease. In Advances in pharmacology and therapeutics I I. Pergamon Press, New York.Google Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • L. N. Simon
    • 1
  • F. K. Hoehler
    • 1
  • D. T. McKenzie
    • 1
  • J. W. Hadden
    • 2
  1. 1.Newport Pharmaceuticals International, Inc.Newport BeachUSA
  2. 2.University of South Florida College of MedicineTampaUSA

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