Skip to main content
Log in

The possible use of spleen cells for the adoptive immunotherapy of cancer patients

  • Original Articles
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

The possible use of spleen-derived mononuclear cells (SPMC) for the intentional and economical adoptive immunotherapy of cancer patients was studied. SPMC were obtained from spleens resected surgically from patients with gastric cancer or idiopathic thrombocytopenic purpura (ITP). When SPMC were cultured in recombinant interleukin 2 (rIL2), SPMC, in the form of interleukin-activated killer spleen cells (IL-SP) proliferated in six of eight cases. CD8+ lymphocytes were the major expanding cell population in most SPMC cultures and IL-SP showed a significant cytolytic activity against cultured tumor cells during cell proliferation. When cultured with a streptococcal preparation, OK-432, for 24 to 48 h, SPMC showed cytotoxic activity against tumor cells and were expressed as OK-432 activated killer spleen cells (OK-SP). The effects of supernatants from IL-SP and OK-SP on tumor cell growth were also examined. The supernatants from IL-SP and OK-SP significantly inhibited cell growth in 3 and 10 out of 11 cases, respectively, while those from OK-SP showed higher growth inhibitory activity than those from IL-SP. The results of this study indicate the potential of SPMC as effector cells for the adoptive immunotherapy of cancer patients.

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

References

  1. Grimm EE, Mazumder A, Zhang HZ, Rosemberg SA (1982) The lymphokine-activated killer cell phenomenon: Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med 155:1823–1841

    Google Scholar 

  2. Lotze MT, Chang AE, Seipp CA, Simpson C, Vetto JT, Rosemberg SA (1986) High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer: Responses, treatment-related morbidity, and histologic findings. JAMA 256:3117–3124

    Google Scholar 

  3. Rosemberg 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 (1987) 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. N Eng J Med 316:889–897

    Google Scholar 

  4. Rosemberg SA (1988) Immunotherapy of cancer using interleukin 2. Immunol Today 9:58–62

    Google Scholar 

  5. Uchida A, Mickshe M (1983) Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and pleural effusion lymphocytes activated by OK-432. J Natl Cancer Inst 71:673–680

    Google Scholar 

  6. Uchida A, Mickshe M (1983) Lysis of fresh human tumor cells by autologous large granular lymphocytes from peripheral blood and pleural effusions. Int J Cancer 32:37–44

    Google Scholar 

  7. De Ley M, Claeys H (1984) Streptococcal preparation OK-432-induced interferon in human leukocytes: Purification and characterization. Int Arch Allergy Appl Immunol 74:21–28

    Google Scholar 

  8. Ichimura O, Suzuki S, Saito M, Sugawara Y, Ishida N (1985) Augumentation of interleukin 1 and interleukin 2 production by OK-432. Int J Immunopharmacol 7:263–270

    Google Scholar 

  9. Katano M, Yamamoto H, Mizoguchi T, Hisatsugu T (1988) Induction of tumor growth inhibitory factor (TGIF) in human mononuclear cells by OK-432, a streptococcal preparation. Cancer Immunol Immunother 27:198–204

    Google Scholar 

  10. Yamamoto A, Nagamuta M, Usami H, Sugawara Y, Watanabe N, Niitsu Y, Urushizaki I (1986) Release of tumor necrosis factor (TNF) into mouse peritoneal fluid by OK-432, a streptococcal preparation. Immunopharmacology 111:79–86

    Google Scholar 

  11. Katano M, Mizoguchi T, Yamamoto H, Nakamura M, Matsuo T, Hisatsugu T, Kisu T, Yamaoka K, Tokunaga O (1990) The antitumor effects of locally injecting human peripheral blood mononuclear cells treated with OK-432 into the tumor site: The possible role of a tumor growth inhibitory factor (TGIF). Jpn J Surg 20:76–82

    Google Scholar 

  12. Toge T, Seto Y, Kuroi K, Yamada H, Aratani K, Fujita T, Yanagawa E, Hattori T (1987) Relationship of the distribution of Leu-2+ cells with suppressor cell activities in the spleen and lymph nodes from gastric cancer. Jpn J Surg 17:72–77

    Google Scholar 

  13. Yanagawa E, Toge T, Sawamura A, Kegoya Y, Baba N, Hattori T (1988) The regulation of natural killer cell activity by splenic nonspecific suppressor cells and its modification in cancer patients. Jpn J Surg 18:660–667

    Google Scholar 

  14. Akiyoshi T, Koba F, Miyazaki S, Arinaga S, Tsuji H (1983) NK activity, TCGF production, and generation of cell-mediated cytotoxicity in spleen cells from gastric cancer patients (in Japanese with English Abstract). Nippon Geka Gakkai Zasshi 84:967–970

    Google Scholar 

  15. Miller SC (1982) Production and renewal of murine natural killer cells in the spleen and bone marrow. J Immunol 129:2282–2286

    Google Scholar 

  16. Fisher RI, Coltman CA, Doroshow JH, Rayner AA, Hawkins MJ, Mier JW, Wiernik P, Mcmannis JD, Weiss GR, Margolin KA, Gemlo BT, Hoth DF, Parkinson DR, Paietta E (1988) Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells: A phase II trial. Ann Intern Med 108:518–523

    Google Scholar 

  17. Kradin RL, Kurnick JT, Lazarus DS, Preffer FI, Dubinett SM, Pinto CE, Gifford J, Davidson E, Grove B, Callahan RJ (1989) Tumor-infiltrating lymphocytes and interleukin-2 in the treatment of advanced cancer. Lancet 18:577–580

    Google Scholar 

  18. Rosemberg SA, Packard BS, Aebersold PM, Solomon D, Toy ST, Simon P, Seipp CA, Simpson C, Charles C, Bock S, Schwartzentruber D, Wei JP, White DE (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma: A preliminary report. New Eng J Med 319:1676–1680

    Google Scholar 

  19. Rosemberg SA, Spiess P, Lafreiere RL (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science (Washington) 233:1318–1321

    Google Scholar 

  20. Damle NK, Doyle LV, Bradley EC (1986) Interleukin-2-activated human killer cells are derived from phenotypically heterogeneous precursors. J Immunol 137:2814–2822

    Google Scholar 

  21. Itoh K, Tilden AB, Kumagai K, Balch CM (1985) Leu-11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin-2 (rIL2)-induced activated killer (AK) cells. J Immunol 134:802–807

    Google Scholar 

  22. Heo DS, Whiteside TL, Johnson JT, Chen K, Barnes EL, Herberman RB (1987) Long-term interleukin-2-dependent growth and cytotoxic activity of tumor-infiltrating lymphocytes from human squamous cell carcinomas of the head and neck. Cancer Res 47:6353–6362

    Google Scholar 

  23. Katano M, Yamamoto H, Mizoguchi T, Iyama A, Matsuo T, Nakamura M, Hisatsugu T, Torisu M (1989) Induction of a tumor growth inhibitory factor (TGIF) in human mononuclear cells by OK-432. Possible clinical use of TGIF. In: Torisu M, Yoshida T (eds) International symposium on new horizons in tumor immunotherapy. Elsevier, Amsterdam, pp 405–416

    Google Scholar 

  24. Katano M, Yamamoto H, Matsuo T, Nakamura M, Mizoguchi T, Hisatsugu T (1989) Clinical significance of tumor growth inhibitory factor (TGIF). In: Proceedings of the 7th International Congress of Immunology, Berlin (abstract)

  25. Katano M, Yamamoto H, Nakamura M, Matsuo T, Hisatsugu T (1990) Synergistic effects of TGIF and interferon γ (IFN γ) on tumor growth. Biotherapy 2:33–40

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Katano, M., Yamamoto, H., Kubota, E. et al. The possible use of spleen cells for the adoptive immunotherapy of cancer patients. Surg Today 23, 13–20 (1993). https://doi.org/10.1007/BF00308994

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00308994

Key Words

Navigation