Experiments were designed to investigate a possible therapeutic role of interleukin-2 (IL-2) gene transfer in the model of murine (EL-4) leukaemia pretreated with cyclophosphamide. It has been found that i.p. pretreatment of the leukaemic mice with cyclophosphamide, followed by i.v. administration of irradiated cells, genetically engineered to produce IL-2 and used as a source of the cytokine (IR-IL-2 cells), cured a substantial percentage of the leukaemic mice. Neither treatment with cyclophosphamide nor administration of the IR-IL-2 cells alone had any significant therapeutic effect. Labelling of the EL-4 and IR-IL-2 cells with different fluorescent cell linkers followed by i.v. injection and detection of the labelled cells in cryostat sections of various organs has shown that both cell populations can be detected almost exclusively in the red pulp of the spleen, close to the white pulp nodules, thus providing the possibility of short-range local interactions among the IL-2-producing cells, IL-2-responsive defence effector cells and EL-4 leukaemia targets.

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague

Zobrazit více v PubMed

Bubeník J (1990) Local and regional immunotherapy of cancer with interleukin 2 (guest editorial). J Cancer Res Clin Oncol 116: 1–7 PubMed PMC

Bubeník J (1993) IL-2 and gene therapy of cancer (Review). Int J Oncol 2: 1049–1052 PubMed

Bubeník J, Indrová M, Perlmann P, Berzins K, Mach O, Kraml J, Toulcová A (1985) Tumour-inhibitory effects of TCGF (IL-2)-containing preparations. Cancer Immunol Immunother 19: 57–61 PubMed PMC

Bubeník J, Voitenok NN, Kieler J, Prassolov VS, Chumakov PM, Bubeníková D, Šímová J, Jandlová T (1988) Local administration of cells containing an inserted IL-2 gene and producing IL-2 inhibits growth of human tumours in PubMed

Bubeník J, Šímová J, Jandlová T (1990) Immunotherapy of cancer using local administration of lymphoid cells transformed by IL-2 DNA and constitutively producing IL-2. Immunol Lett 23: 287–292 PubMed

Bubeník J, Lotzová E, Indrová M, Šímová J, Jandlová T, Savary CA (1991) IL-2 gene transfer in immunotherapy of cancer: local administration of LAK and X63-m-IL-2 cells transformed by IL-2 cDNA and constitutively producing IL-2 inhibits growth of plasmacytomas in syngeneic mice. Nat Immun Cell Growth Regul 10: 247–255 PubMed

Cheever MA, Greenberg PD, Gillis S, Fefer A (1982) Specific adoptive therapy of murine leukemia with cells sensitized in vitro and expanded by culture with interleukin 2. Prog Cancer Res Ther 22: 127–146

Foa R, Guarini A, Gansbacher B (1992) IL-2 treatment for cancer: from biology to gene therapy. Br J Cancer 66: 992–998 PubMed PMC

Gansbacher B, Zier K, Cronin K, Hantzopoulos PA, Bouchard B, Houghton A, Gilboa E, Golde D (1992) Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-γ in irradiated human melanoma cells. Blood 80: 2817–2825 PubMed

Gorer PA, Amos DB (1956) Passive immunity of mice against C57BL leukosis EL-4 by means of iso-immune serum. Cancer Res 16: 338–343 PubMed

Karasuyama H, Melchers F (1988) Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4, or 5 using modified cDNA expression vectors. Eur J Immunol 18: 97–104 PubMed

Kearney JF, Radbruch A, Liesegang B, Rajewsky K (1979) A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol 123: 1548–1550 PubMed

Kedar E, Klein E (1992) Cancer immunotherapy: are the results discouraging? Can they be improved? Adv Cancer Res 59: 245–322 PubMed

Lee K, O'Donnell RW, Marquis D, Cockett ATK (1988) Eradication of palpable intradermal murine bladder tumours by systemic interleukin-2 and cyclophosphamide in C3H mice. J Biol Response Mod 7: 32–42 PubMed

Naito K, Pellis NR, Kahan BD (1988) Effect of continuous administration of interleukin 2 on active specific chemoimmunotherapy with extracted tumor-specific transplantation antigen and cyclophosphamide. Cancer Res 48: 101–108 PubMed

Rosenberg SA, Lotze MT, Yang JC, Aebersold PM, Linehan WM, Seipp CA, White DE (1989) Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg 210: 474–484 PubMed PMC

Šímová J, Bubeník J, Voitenok NN, Gren E (1989) Chemoimmunotherapy of MC-induced mouse sarcomas with human recombinant interleukin 2 and cyclophosphamide: age-dependent decline of the therapeutic efficacy. Folia Biol (Praha) 35: 137–142 PubMed

Vallera DA, Taylor PA, Aukerman SL, Blazar BR (1993) Antitumor protection from the murine T-cell leukemia/lymphoma EL-4 by the continuous subcutaneous coadministration of recombinant macrophage-colony stimulating factor and interleukin-2. Cancer Res 53: 4273–4280 PubMed