Skip to main content
Log in

Therapeutic efficacy of sequential therapy with OK-432, cyclophosphamide, IL2-cultured lymphocytes andin vivo IL2 against advanced murine plasmacytoma

  • Published:
Biotherapy

Summary

BALB/c mice inoculated IP with a syngeneic plasmacytoma MOPC 104E were treated with a combination of a streptococcal preparation, OK-432 (1 KE, 0.1 mg/mouse), low-dose of cy clophosphamide (CPA, 1 mg/kg) and adoptive transfer of tumor-bearer-spleen cells (2 x 10' cells) cultured with IL2 and sonicated tumor extract (adoptive immunotherapy; AIT). The consecutive protocol of OK-432 (day 8, 9 post inoculation) — CPA (day 10) — AIT (day 11) was the most effective. Rate of complete remission was highest when recombinant (r-) IL2 was injected to the mice after AIT. Moreover, another bacterial preparation,Nocardia rubra cell wall skeleton and another low-dose chemotherapy, Mitomycin C could be used successfully instead of OK-432 or CPA. Transfer test of intraperitoneal cells (tumor cells plus host cells) of mice on day 11 post inoculation (on the day of AIT) revealed that OK-432 augmented the susceptibility of peritoneal cells to cultured lymphocytes in inhibition of transplantability, and that CPA after OK-432 augmented the anti-tumor effect of tumor-bearer-spleen cells which act synergistically with cultured lymphocytes. This therapy schedule seems to be the best model to augment the effect of AIT with minimal side effect.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

AIT:

adoptive immunotherapy

CL:

cultured lymphocytes

References

  1. Cheever MA, Greenberg PD, Fefer A. Specific adoptive therapy of established leukemia with syngeneic lymphocytes sequentially immunized in vivo and in vitro and nonspecifically expanded by culture with interleukin 2. J Immunol 126: 1318–22, 1981.

    Google Scholar 

  2. Eberlein TJ, Rosenstein M, Spiess P, Wesley R, Rosenberg SA. Adoptive chemoinununotherapy of a syngeneic murine lymphoma with long-term lymphoid cell lines expanded in T cell growth factor. Cancer Immunol Immunother 13: 5–13, 1982.

    Google Scholar 

  3. Cheever MA, Greenberg PD, Fefer A, Gillis S. Augmentation of the anti-tumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2. J Exp Med 155: 968–80, 1982.

    Google Scholar 

  4. Kan N, Ohgaki K, Inamoto T, Kodama H. Antitumor and therapeutic effects of spleen cells from tumor-bearing mice cultured with T cell growth factor and soluble tumor extract. Cancer Immunol Immunother 18: 215–22, 1984.

    Google Scholar 

  5. Kan N, Inamoto T, Hori T, Nio Y, Tsuchitani T, Kodama H, Tobe T, Ohgaki K. Adoptive immunotherapy of murine tumor using cultured syngeneic tumor-bearer spleen cells: Therapeutic effect of cultured lymphocytes against malignant ascites and its augmentation by streptococcal preparation, OK-432. J Jpn Soc Cancer Ther 20: 784–96, 1985.

    Google Scholar 

  6. Kan N, Hori T, Okino T, Imai S, Ohgaki K, Tobe T. Synergistic anti-tumor effect of host's lymphocytes and lymphocytes cultured with IL-2 in OK-432-combined adoptive immunotherapy. Abstract of the 14th International Cancer Congress (1): 144, 1986.

  7. Masuno T, Hayashi S, Ito M, Ikeda T, Ogura T, Kishimoto S, Yamamura Y. Mechanism(s) of in vitro macrophage activation with Nocardia rubra cell wall skeleton: The effects on macrophage activating factor production by lymphocytes. Cancer Immunol Immunother 22: 132–38, 1986.

    Google Scholar 

  8. Koyama S, Ozaki A, Iwasaki Y, Sakita T, Osuga T, Watanabe A, Suzuki M, Kawasaki T, Soma T, Tabuchi T, Nakayama N, Koizumi S, Yokoyama K, Uchida T, Orii K, Tanaka T. Randomized controlled study of postoperative adjuvant immunotherapy with Nocardia rubra cell wall skeleton (N-CWS) and Tegafur for gastric carcinoma. Cancer Immunol Immunother 22: 148–54, 1986.

    Google Scholar 

  9. Taguchi T, Urushizaki T, Koyama I, Saito T, Niijima T, Takakura K, Izuo M, Ikeda S, Kondo T, Kimura K, Ohta K, Akaboshi Y, Ogura T, Hattori T. Phase 1 trial of recombinant interleukin-2 (TGP-3). In: Ishigame J, eds. Recent advances in chemotherapy. Tokyo: Tokyo University Press, 1985, 804–5.

    Google Scholar 

  10. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. New Engl J Med 316: 889–97, 1987.

    Google Scholar 

  11. Hattori T, Yamamoto S, Satoh H, Funasaka M, Furue H. Experimental and clinical studies on combination therapy of anticancer drugs with OK-432. Jpn J Cancer Clin 19: 929–34, 1973.

    Google Scholar 

  12. Koshimura S, Ryoyama K. Enhancement of antileukemic effect in the combination of 5-fluorouracil and OK-432. Cancer Treat Rep 61: 17–27, 1977.

    Google Scholar 

  13. Saito M, Sugawara Y, Ogawa H, Ota K. Combined effect of intraperitoneally administered adriamycin and OK-432 against Meth-A ascites tumor. Jpn J Cancer Chemother 6: 1101–7, 1979.

    Google Scholar 

  14. Hanna MG, Key ME. Immunotherapy of metastases enhances subsequent chemotherapy. Science 217: 367–9, 1982.

    Google Scholar 

  15. Lubet RA, Carlson DE. Tumor immunity directed against MOPC104E: Effect of various therapeutic regimens. Cancer Immunol Immunother 2: 267–70, 1977.

    Google Scholar 

  16. Torisu M, Katano M, Kimura Y, Itoh H, Takesue M. New approach to management of malignant ascites with a streptococcal preparation, OK-432. 1. Improvement of host immunity and prolongation of survival. Surgery 93: 357–64, 1983.

    Google Scholar 

  17. Kan N, Okino T, Nakanishi M, Satoh K, Ohgaki K, Tobe T.In vivo andin vitro synergistic anti-tumor effect of IL2-cultured tumor-bearer-spleen cells and immune fresh spleen cells. Cancer Immunol Immunother 28: 260–6, 1989.

    Google Scholar 

  18. Mills GD, North RJ. Expression of passively transferred immunity against an established tumor depends on generation of cytolytic T cells in recipient: Inhibition by suppressor cells. J Exp Med 157: 1448–60, 1983.

    Google Scholar 

  19. Rosenstein M, Eberline TJ, Rosenberg SA. Adoptive immunotherapy of established syngeneic solid tumors: Role of T lymphoid populations. J Immunol 132: 2117–22, 1984.

    Google Scholar 

  20. Hori T, Kan N, Nio Y, Tsuchitani T, Inamoto T, Kodama H, Tobe T. Augmentation by OK-432 of cytotoxic activities of lymphocytes in carcinomatous pleural effusions, and its application for adoptive immunotherapy. In: Tobe T, eds. New applications of OK-432. Tokyo: Exerpta Medica, 1986: 132–40.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kan, N., Okino, T., Nakanishi, M. et al. Therapeutic efficacy of sequential therapy with OK-432, cyclophosphamide, IL2-cultured lymphocytes andin vivo IL2 against advanced murine plasmacytoma. Biotherapy 1, 197–206 (1989). https://doi.org/10.1007/BF02170888

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02170888

Key words

Navigation