Skip to main content
SpringerLink
Log in

Effect of recombinant interleukin 2 (R-IL2) on in vivo growth of murine myeloma X5563

  • Original Articles
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

The present study deals with the effect of recombinant interleukin 2 (R-IL2) on in vivo growth of murine myeloma X5563. Administration of R-IL2 (5×104 J.U./mouse per day) s.c. starting 1 day after X5563 inoculation i.d. had a marginal effect on the growth of X5563, and all the mice repeatedly given R-IL2 from day 1 to day 17 died. However, daily administration of R-IL2 starting 7 days after the tumor inoculation was highly effective and significantly lengthened survival time compared with the control mice injected with vehicle alone. About 50% of the treated mice were completely cured, and survived for more than a month after the therapy ceased. In a representative experiment, where the growth of X5563 was slow because of the small number of inoculated tumor cells, all the mice (n=6) given R-IL2 from day 11 to day 23 showed complete cure of the established X5563 solid tumor. These mice showed in vivo protective immunity and in vitro cytotoxic T cell responses to X5563 tumor antigens. Histologically, a large number of macrophages and lymphocytes had infiltrated the area around the necrotic X5563 tumor mass in the mice which had received R-IL2 therapy. These results suggest that repeated injections of R-IL2 at the local site after tumor development can augment antitumor immunological responses and subsequently induce tumor regression.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bubenik J, Perlmann P, Indrora M, Simora J, Jandlova T, Neuwirt J (1983) Growth inhibition of an MC-induced mouse sarcoma by TCGF (IL2)-containing preparations. Cancer Immunol Immunother 14:205

    Google Scholar 

  2. Cheever MA, Greenberg PD, Fefer A, Gillis S (1982) 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

    Google Scholar 

  3. Cheever MA, Greenberg PD, Irle C, Thompson JA, Henney CS, Gillis S (1984) Interleukin 2 administered in vivo induces the growth of cultured T cell in vivo. J Immunol 132:2259

    Google Scholar 

  4. Donohue JH, Rosenstein M, Chang AE, Lotze MT, Robb RJ, Rosenberg SA (1984) The systemic administration of purified interleukin 2 enhances the ability of sensitized murine lymphocytes to cure a disseminated syngeneic lymphoma. J Immunol 132:2123

    Google Scholar 

  5. Eberlein TJ, Rosenstein MR, Rosenberg SA (1982) Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2. J Exp Med 156:385

    Google Scholar 

  6. Farrar WL, Johnson HM, Farrar JJ (1981) Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin 2. J Immunol 126:1120

    Google Scholar 

  7. Forni G, Giovarelli M, Santoni A (1985) Lymphokine-activated tumor inhibition in vivo. I. The local administration of interleukin 2 triggers nonreactive lymphocytes from tumor-bearing mice to inhibit tumor growth. J Immunol 134:1305

    Google Scholar 

  8. Fujiwara H, Hamaoka T, Teshima K, Aoki H, Kitagawa M (1976) Preferential generation of killer or helper T lymphocyte activity directed to the tumor-associated transplantation antigens. Immunology 31:239

    Google Scholar 

  9. Fujiwara H, Hamaoka T, Shearer GM, Yamamoto H, Terry WD (1980) The augmentation of in vitro and in vivo tumor-specific T cell-mediated immunity by amplified T lymphocytes. J Immunol 124:863

    Google Scholar 

  10. Fujiwara H, Moriyama Y, Suda T, Tsuchida T, Shearer GM, Hamaoka T (1984) Enhanced TNP-reactive helper T cell activity and its utilization in the induction of amplified tumor immunity that results in tumor regression. J Immunol 132:1571

    Google Scholar 

  11. Fujiwara H, Fukuzawa M, Yoshioka T, Nakajima H, Hamaoka T (1984) The role of tumor-specific Lyt 1+2−-T cells in vivo. 1) Lyt1+2− T cells do not necessarily require recruitment of host's cytotoxic T cell precursors for implementation of in vivo immunity. J Immunol 133:1671

    Google Scholar 

  12. Gillis S, Smith KA (1977) Long-term culture of tumor-specific cytotoxic T cells. Nature 268:154

    Google Scholar 

  13. Gillis S, Ferm MM, Ou W, Smith K (1978) T cell growth factor: Parameters of production and a quantitative microassay for activity. J Immunol 120:2027

    Google Scholar 

  14. Greenberg PD, Cheever MA, Fefer A (1981) Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt 1+2− lymphocytes. J Exp Med 154:952

    Google Scholar 

  15. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA (1982) 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

    Google Scholar 

  16. Grimm EA, Ramey KM, Mazumder A, Wilson DJ, Djeu JY, Rosenberg SA (1983) Lymphokine-activated killer cell phenomenon. 2) Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells. J Exp Med 157:884

    Google Scholar 

  17. Hefeneider SH, Conlon PJ, Henney CS, Gillis S (1983) In vivo interleukin 2 administration augments the generation of alloreactive cytolytic T lymphocytes and resident natural killer cells. J Immunol 130:222

    Google Scholar 

  18. Henney CS, Kuribayashi K, Kern DE, Gillis S (1981) Interleukin 2 augments natural killer cell activity. Nature 291:335

    Google Scholar 

  19. Howard M, Matis L, Malek TR, Shevach E, Kell W, Cohen D, Nakanishi K, Paul WE (1983) Interleukin 2 induces antigen-reactive T cell lines to secrete BCGF-1. J Exp Med 158:2024

    Google Scholar 

  20. Mazumder A, Rosenberg SA (1984) Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2. J. Exp Med 159:495

    Google Scholar 

  21. Morgan DA, Ruscetti FW, Gallo RC (1976) Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 193:1007

    Google Scholar 

  22. Mule JJ, Shu S, Schwarz SL, Rosenberg SA (1984) Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin 2. Science 225:1487

    Google Scholar 

  23. Rosenberg SA, Grimm EA (1984) Biological activity of recombinant human interleukin 2 produced in Escherichia coli. Science 223:1412

    Google Scholar 

  24. Rosenberg SA, Mule JJ, Spiess PJ, Reichert CM, Schwatz SL (1985) Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin 2. J Exp Med 161:1169

    Google Scholar 

  25. Rosenstein M, Yron I, Kaufmann Y, Rosenberg SA (1983) Lymphokine-activated killer cells: Lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in Interleukin 2. Cancer Res 44:1946

    Google Scholar 

  26. Taniguchi T, Matsui H, Fujita T, Takaoka C, Kashima N, Yoshimoto R, Hamuro J (1983) Structure and expression of a cloned cDNA for human interleukin 2. Nature 302:305

    Google Scholar 

  27. Wagner H, Hardt C, Heeq K, Rollinghoff M, Pfizenmaier K (1980) T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice. Nature 284:278

    Google Scholar 

  28. Yutoku M, Senoh H, Watanabe S, Matsuoka Y, Kitagawa M (1972) Quantitation of in vivo growth plasmacytoma X5563 by immunoassay for its paraprotein with individual antigeneic specificity. J Natl Cancer Inst 49:1395

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Shionogi Research Laboratories, Shionogi & Co., Ltd., Fukushima-ku, 553, Osaka, Japan

    Ryuji Maekawa, Mitsunobu Matsumoto, Taeko Kitagawa, Minoru Harada & Kosaburo Sato

Authors
  1. Ryuji Maekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mitsunobu Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taeko Kitagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Minoru Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kosaburo Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maekawa, R., Matsumoto, M., Kitagawa, T. et al. Effect of recombinant interleukin 2 (R-IL2) on in vivo growth of murine myeloma X5563. Cancer Immunol Immunother 23, 25–30 (1986). https://doi.org/10.1007/BF00205551

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00205551

Keywords

Search

Navigation