Use of IL-2 gene transfer in local immunotherapy of cancer.
Insertion of functional interleukin-2 (IL-2) gene into a plasmacytoma cell line X63-Ag8.653 substantially reduced tumorigenicity of the resulting cloned cells, designated as X63-m-IL-2. Peritumoral administration of the X63-m-IL-2 cells, producing constitutively large quantities of IL-2, resulted in regressions of established X63-Ag8.653 plasmacytomas growing in the peritoneal cavity of syngeneic mice. In vitro activation of BALB/c spleen cells by co-culture with X63-m-IL-2 cells or their supernatants gave rise to cytotoxic lymphocytes with lymphokine-activated killer (LAK) activity against syngeneic X63-Ag8.653 plasmacytoma and other tumor targets. In contrast, peritumoral administration of X63-Ag8.653 cells carrying an inserted interleukin-4 (IL-4) gene (designated X63-m-IL-4 cells) and producing constitutively large quantities of IL-4 did not result in a therapeutic effect. Moreover, the admixture of the X63-m-IL-4 and X63-m-IL-2 cells substantially diminished the X63-m-IL-2 cell-mediated therapeutic effect. Similarly, IL-4-containing supernatants generated from X63-m-IL-4 cell cultures substantially diminished LAK activation by X63-m-IL-2 cell produced supernatants.
Bubeník
J
J
Institute of Molecular Genetics, Czechoslovak Academy of Sciences, Prague.
Lotzová
E
E
Indrová
M
M
Símová
J
J
Jandlová
T
T
Bubeníková
D
D
D000818:Animals; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010954:Plasmacytoma / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D015847:Interleukin-4