Skip to main content
PMC home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1986 Sep;23(1):25–30. doi: 10.1007/BF00205551

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

Ryuji Maekawa 1, Mitsunobu Matsumoto 1, Taeko Kitagawa 1, Minoru Harada 1, Kosaburo Sato 1,✉
PMCID: PMC11038606  PMID: 3490306

Abstract

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.

Keywords: Myeloma, Cell Response, Control Mouse, Tumor Development, Marginal Effect

References

  • 1.Bubenik J, Perlmann P, Indrora M, Simora J, Jandlova T, Neuwirt J. Growth inhibition of an MC-induced mouse sarcoma by TCGF (IL2)-containing preparations. Cancer Immunol Immunother. 1983;14:205. doi: 10.1007/BF00205362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.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. 1982;155:968. doi: 10.1084/jem.155.4.968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Cheever MA, Greenberg PD, Irle C, Thompson JA, Henney CS, Gillis S. Interleukin 2 administered in vivo induces the growth of cultured T cell in vivo . J Immunol. 1984;132:2259. [PubMed] [Google Scholar]
  • 4.Donohue JH, Rosenstein M, Chang AE, Lotze MT, Robb RJ, Rosenberg SA. The systemic administration of purified interleukin 2 enhances the ability of sensitized murine lymphocytes to cure a disseminated syngeneic lymphoma. J Immunol. 1984;132:2123. [PubMed] [Google Scholar]
  • 5.Eberlein TJ, Rosenstein MR, Rosenberg SA. Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2. J Exp Med. 1982;156:385. doi: 10.1084/jem.156.2.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Farrar WL, Johnson HM, Farrar JJ. Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin 2. J Immunol. 1981;126:1120. [PubMed] [Google Scholar]
  • 7.Forni G, Giovarelli M, Santoni A. 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. 1985;134:1305. [PubMed] [Google Scholar]
  • 8.Fujiwara H, Hamaoka T, Teshima K, Aoki H, Kitagawa M. Preferential generation of killer or helper T lymphocyte activity directed to the tumor-associated transplantation antigens. Immunology. 1976;31:239. [PMC free article] [PubMed] [Google Scholar]
  • 9.Fujiwara H, Hamaoka T, Shearer GM, Yamamoto H, Terry WD. The augmentation of in vitro and in vivo tumor-specific T cell-mediated immunity by amplified T lymphocytes. J Immunol. 1980;124:863. [PubMed] [Google Scholar]
  • 10.Fujiwara H, Moriyama Y, Suda T, Tsuchida T, Shearer GM, Hamaoka T. Enhanced TNP-reactive helper T cell activity and its utilization in the induction of amplified tumor immunity that results in tumor regression. J Immunol. 1984;132:1571. [PubMed] [Google Scholar]
  • 11.Fujiwara H, Fukuzawa M, Yoshioka T, Nakajima H, Hamaoka T. 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. 1984;133:1671. [PubMed] [Google Scholar]
  • 12.Gillis S, Smith KA. Long-term culture of tumor-specific cytotoxic T cells. Nature. 1977;268:154. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  • 13.Gillis S, Ferm MM, Ou W, Smith K. T cell growth factor: Parameters of production and a quantitative microassay for activity. J Immunol. 1978;120:2027. [PubMed] [Google Scholar]
  • 14.Greenberg PD, Cheever MA, Fefer A. Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt 1+2− lymphocytes. J Exp Med. 1981;154:952. doi: 10.1084/jem.154.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. 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. 1982;155:1823. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Grimm EA, Ramey KM, Mazumder A, Wilson DJ, Djeu JY, Rosenberg SA. 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. 1983;157:884. doi: 10.1084/jem.157.3.884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Hefeneider SH, Conlon PJ, Henney CS, Gillis S. In vivo interleukin 2 administration augments the generation of alloreactive cytolytic T lymphocytes and resident natural killer cells. J Immunol. 1983;130:222. [PubMed] [Google Scholar]
  • 18.Henney CS, Kuribayashi K, Kern DE, Gillis S. Interleukin 2 augments natural killer cell activity. Nature. 1981;291:335. doi: 10.1038/291335a0. [DOI] [PubMed] [Google Scholar]
  • 19.Howard M, Matis L, Malek TR, Shevach E, Kell W, Cohen D, Nakanishi K, Paul WE. Interleukin 2 induces antigen-reactive T cell lines to secrete BCGF-1. J Exp Med. 1983;158:2024. doi: 10.1084/jem.158.6.2024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Mazumder A, Rosenberg SA. 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. 1984;159:495. doi: 10.1084/jem.159.2.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Morgan DA, Ruscetti FW, Gallo RC. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976;193:1007. doi: 10.1126/science.181845. [DOI] [PubMed] [Google Scholar]
  • 22.Mule JJ, Shu S, Schwarz SL, Rosenberg SA. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin 2. Science. 1984;225:1487. doi: 10.1126/science.6332379. [DOI] [PubMed] [Google Scholar]
  • 23.Rosenberg SA, Grimm EA. Biological activity of recombinant human interleukin 2 produced in Escherichia coli . Science. 1984;223:1412. doi: 10.1126/science.6367046. [DOI] [PubMed] [Google Scholar]
  • 24.Rosenberg SA, Mule JJ, Spiess PJ, Reichert CM, Schwatz SL. Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin 2. J Exp Med. 1985;161:1169. doi: 10.1084/jem.161.5.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Rosenstein M, Yron I, Kaufmann Y, Rosenberg SA. Lymphokine-activated killer cells: Lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in Interleukin 2. Cancer Res. 1983;44:1946. [PubMed] [Google Scholar]
  • 26.Taniguchi T, Matsui H, Fujita T, Takaoka C, Kashima N, Yoshimoto R, Hamuro J. Structure and expression of a cloned cDNA for human interleukin 2. Nature. 1983;302:305. doi: 10.1038/302305a0. [DOI] [PubMed] [Google Scholar]
  • 27.Wagner H, Hardt C, Heeq K, Rollinghoff M, Pfizenmaier K. T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice. Nature. 1980;284:278. doi: 10.1038/284278a0. [DOI] [PubMed] [Google Scholar]
  • 28.Yutoku M, Senoh H, Watanabe S, Matsuoka Y, Kitagawa M. Quantitation of in vivo growth plasmacytoma X5563 by immunoassay for its paraprotein with individual antigeneic specificity. J Natl Cancer Inst. 1972;49:1395. [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES