Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Changes in immunological parameters in lung cancer patients undergoing immunotherapy with streptococcal preparation OK-432

Summary

We have studied the immunological status of patients treated with streptococcal preparation OK-432. Two KE of OK-432 was injected intramuscularly once every week for more than three years unless the patients died. The natural killer (NK) activity in those patients who underwent curative surgery for lung cancer and had no sign of recurrence was significantly increased (P < 0.01) during the OK-432 treatment. However, the NK activity in the patients who had persistent disease (non-resected cases, incompletely resected cases or recurrent cases) was not significantly increased in comparison with that before the immunotherapy. Also, in the cases with no clinical symptoms of recurrence, both the lymphoblastogenetic reactions to the mitogens and the IL-2 production were significantly enhanced(P < 0.01) during the administration of OK-432. Reactions in the SU-PS (polysaccharide taken from the cell-wall fraction of theStreptococcus pyogenes SU strain and containing 7.2% of protein) skin-test appeared to significantly correlate with the immunological status of the patients under OK-432 therapy, but the PHA and PPD skin reactions showed no definitive enhancement. The survival rate of the patients whose SU-PS skin tests were positive during the OK-432 immunotherapy was significantly higher (P < 0.01) than that of the patients with negative reactions.

This is a preview of subscription content, log in to check access.

Abbreviations

BRM:

biological response modifiers

Con A:

concanavarin A

IL-2:

interleukin-2

NED:

no evidence of disease

NK cell:

natural killer cell

PBL:

peripheral blood lymphocytes

PHA:

phytohemagglutinin

PPD:

rpurified protein derivative

PWM:

Pokeweed mitogen

S.I.:

stimulation index

SU-PS:

SU-polysaccharide

References

  1. 1.

    Watanabe Y, Iwa T. Clinical value of immunotherapy for lung cancer by the streptococcal preparation OK-432. Cancer 1984; 53: 248–53.

  2. 2.

    Watanabe Y, Iwa T. Clinical value of immunotherapy by streptococcal preparation, OK-432, for lung cancer: A randomized study. In Hoshino T, Uchida A, eds: Clinical and experimental studies in immunotherapy. Amsterdam, Current Clinical Practice Series No. 17. Excerpta Medica, Amsterdam 1984; 120–37.

  3. 3.

    Watanabe Y, Iwa T. Immunotherapy of lung cancer: A randomized clinical trial of OK-432 immunotherapy and a review of the literature on nonspecific immunotherapy. Int J Immunother 1986; 2: 51–67.

  4. 4.

    Watanabe Y, Iwa T. Clinical value of immunotherapy for lung cancer by the Streptococcal preparation OK-432. J Biol Response Mod 1987; 6: 169–80.

  5. 5.

    McKneally MF, Maver C, Lininger L, Kausel HW, McIlduff JB, Older TM, Foster ED, Alley RD. Four-year follow-up on the Albany experience with intrapleural BCG in lung cancer. J Thorac Cardiovasc Surg 1981; 81: 485–92.

  6. 6.

    Yasumoto K, Manabe H, Ueno M, Ohta M, Ueda H, Iida A, Nomoto K, Azuma I, Yamamura Y. Immunotherapy of human lung cancer with BCG cell-wall skeleton. Gann 1976; 67: 787–95.

  7. 7.

    Israel L, Depierre A, Choffel C, Milleron B, Eldstein R. Immunochemotherapy in 34 cases of oat cell carcinoma of the lung with 19 complete response. Cancer Treat Rep 1977; 61: 343–47.

  8. 8.

    Amery WK. Final results of a multicenter placebocontrolled Levamisole study of resectable lung cancer. Cancer Treat Rep 1978; 62: 1677–83.

  9. 9.

    Colotta F, Rambaldi A, Colombo N, Tabacchi L, Introna M, Mantovani A. Effect of a streptococcal preparation (OK-432) on natural killer activity of tumor-associated lymphoid cells in human ovarian carcinoma and lysis of fresh ovarian tumour cells. Brit J Cancer 1983; 48: 515–25.

  10. 10.

    Uchida A, Micksche M. Intrapleural administration of OK-432 in cancer patients: Activation of NK cells and reduction of suppressor cells. Int J Cancer 1983; 31: 1–5.

  11. 11.

    Christmas SE, Meager A, Moore M. Studies of the enhancement of natural cytotoxicity by the streptococcal immunopotentiator OK-432. Int J Immunopharmac 1986; 8: 83–92.

  12. 12.

    Negishi Y, Miura M, Saito M, Sano Y, Akiya K, Fujisawa Y. Studies of natural killer activity and augmentation by OK-432 in patients with gynecological malignancies. Gynecol Obstet Invest 1986; 21: 40–46.

  13. 13.

    Wakasugi H, Kasahara T, Minato N, Hamuro J, Miyata M, Morioka Y.In vitro potentiation of human natural killer cell activity by a streptococcal preparation, OK-432: Interferon and interleukin-2 participation in the stimulation with OK-432. J Nat Cancer Inst 1982; 69: 807–12.

  14. 14.

    Uchida A. Augmentation of autologous tumor killing activity of tumor-associated large granular lymphocytes by the streptococcal preparation OK-432. Meth and Find Exptl Clin Pharmacol 1986; 8: 81–4.

  15. 15.

    Uchida A, Micksche M, Hoshino T. Intrapleural administration of OK-432 in cancer patients: Augmentation of autologous tumor killing activity of tumor-associated large granular lymphocytes. Cancer Immunol Immunother 1984; 18: 5–12.

  16. 16.

    Noda T, Asano M, Yoshie O, Suzuki R, Ebina T, Ishida N. Interferon-γ induction in human peripheral blood mononuclear cells by OK-432, a killed preparation of streptococcus pyogenes. Microbiol Immunol 1986; 30: 81–8.

  17. 17.

    Fukui H, Koishihara Y, Nagamuta M, Mizutani Y, Uchida A. Production of interleukin 6 by human spleen cells stimulated with streptococcal preparation OK-432. Immunology Letters 1989; 21: 127–30.

  18. 18.

    Uchida A, Hoshino T. Clinical studies on cell-mediated immunity in patients with malignant disease. I. Effect of immunotherapy with OK-432 on lymphocyte subpopulation and phytomitogen responsiveness in vitro. Cancer 1980; 45: 476–83.

  19. 19.

    Yagi Y, Yagi S. Immunotherapy of patients with terminalstage malignant tumors with an immunopotentiator OK-432 — A comparison of SU-PS test-responding and-nonresponding patients. Int J Immunopharmac 1988; 10: 451–61.

  20. 20.

    Cervical Cancer Immunotherapy Study Group: Immunotherapy using the streptococcal preparation OK-432 for the treatment of uterine cervical cancer. Cancer 1987; 60: 2394–2402.

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Watanabe, Y., Shimizu, J., Hashizume, Y. et al. Changes in immunological parameters in lung cancer patients undergoing immunotherapy with streptococcal preparation OK-432. Biotherapy 2, 235–245 (1990). https://doi.org/10.1007/BF02173525

Download citation

Key words

  • immunotherapy
  • lung cancer
  • OK-432
  • streptococcal preparation
  • immunological parameter
  • SU-polysaccharide skin test