Abstract
It has been previously found that local administration of Balb/c plasmacytoma cells transformed and made non-tumorigenic by insertion of the cloned murine interleukin-2 (IL-2) gene induced regressions of a variety of murine tumours including the original Balb/c plasmacytoma X63-Ag8.653 growing in syngeneic mice. The tumour-inhibitory effect of the plasmacytoma cells transformed by IL-2 cDNA and designated as X63-m-IL-2 was due to their high constitutive production of IL-2. Here we show that admixture of syngeneic spleen cells to the X63-m-IL-2 transformants substantially (P<0.025) increased the antitumour efficacy of the transformants. Balb/c spleen cells co-cultivated with X63-m-IL-2 cells in vitro yielded predominantly Thy 1.2+, CD3+, LFA-1+ lymphocytes, cytolytic for the X63-Ag8.653 plasmacytoma as well as for other murine tumours, including the X63-m-IL-2 target cells.
This is a preview of subscription content, log in via an institution to check access.
Abbreviations
- IL-2:
-
interleukin-2
- LAK:
-
lymphokine-activated killer
- NK:
-
natural killer
- HPRT:
-
hypoxanthine phosphoribosyl transferase
- HAT:
-
hypoxanthine/aminopterin/thymidine
References
Blankenstein T, Qin Z, Überla K, Müller T, Rosen H, Volk H-D, Diamantstein T (1991) Tumor suppression after tumor cell-target tumor necrosis factor alpha gene transfer. J Exp Med 173:1047–1052
Bubeník J (1990) Local and regional immunotherapy of cancer with interleukin 2 (guest editorial). J Cancer Res Clin Oncol 116:1–7
Bubeník J, Indrová M (1987) The anti-tumour efficacy of human recombinant interleukin-2: correlation between sensitivity of tumours to the cytolytic effect of LAK cells in vitro and their susceptibility to interleukin-2 immunotherapy in vivo. Cancer Immunol Immunother 24:269–271
Bubeník J, Šímová J, Jandlová T (1989/1990) Immunotherapy of cancer using local administration of lymphoid cells transformed by IL-2 cDNA and constitutively producing IL-2. Immunol Lett 23:287–292
Bubeník J, Lotzová E, Zeuthen J, Bubeníková D, Šímová J, Indrová M (1991) Gene therapy of cancer: use of interleukin-2 (IL-2) gene transfer in local immunotherapy. J Exp Clin Cancer Res 10:213–220
Bubeník J, Zeuthen J, Šímová J, Jandlová T, Bubeníková D, Radzikowski C (1992) Activation and phenotyping of LAK generated by exposure to product of cells transformed by interleukin 2 cDNA. Anticancer Res 12:965–968
Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, Frost P (1990) Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60:397–403
Gansbacher B, Zier K, Daniels B, Cronin K, Bannerji R, Gilboa E (1990) Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 172:1217–1224
Goldie H, Butler Ch, Anderson MM (1953) Growth characteristics of free C1498 (granulocytic leukemia) tumor cells in the peritoneal fluid and the blood of C57 mice. Cancer Res 13:125–129
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
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
Kedar E, Herberman RB (1982) Induction of NK-like anti-tumor reactivity in vitro and in vivo by IL-2. In: Herberman RB (ed) NK cells and other natural effector cells. Academic Press. New York, pp 859–861
Mulé JJ, Yang J, Shu S, Rosenberg SA (1986) The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: direct correlation between reduction of established metastases and cytolytic activity of lymphokine-activated killer cells. J Immunol 136:3899–3903
Rosenberg S, Lotze MT (1986) Cancer immunotherapy using interleukin-2 and interleukin-2-activated lymphocytes. Annu Rev Immunol 4:681–713
Tepper RI, Pattengale PK, Leder P (1989) Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell 57:503–512
Wigzell H, Ramstedt U (1986) Natural killer cells. In: Weyr MM (ed) Cellular immunology, vol 2. Blackwell Scientific, Oxford, pp 601–609
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bubeník, J., Šímová, J., Bubeníková, D. et al. Utilization of interleukin-2 gene transfer in local immunotherapy of cancer. J Cancer Res Clin Oncol 119, 253–256 (1993). https://doi.org/10.1007/BF01212720
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01212720