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PubMedDate not supplied

Activation and phenotyping of LAK generated by exposure to product of cells transformed by interleukin 2 cDNA.

It has been previously found that local administration of X63-m-IL-2 cells transformed by interleukin 2 (IL-2) cDNA and constitutively producing large quantities of IL-2 mediated regressions of murine plasmacytomas and 3-methyl-cholanthrene-induced sarcomas transplanted in syngeneic mice. Here we show that killer cells generated by cultivation of spleen cells in supernatants from X63-m-IL-2 cultures (LAK) or by co-cultivation of murine splenocytes with X63-m-IL-2 cells were cytolytic for natural killer (NK)-sensitive as well as NK-resistant target cells, including the IL-2-producing X63-m-IL-2 cells. Spleen cells cultured in X63-m-IL-2 supernatants or co-cultivated with X63-m-IL-2 cells yielded predominantly Thy 1.2+, CD3+, LFA-1+ lymphocytes. The in vitro results suggest that the LAK cells generated due to the IL-2 production by genetically engineered cells probably help to terminate the treatment by killing the IL-2 producers.

Animals↗

PubMedDate not supplied

Gene therapy of cancer: use of IL-2 gene transfer and kinetics of local T and NK cell subsets.

Experiments were designed to compare the efficacy of recombinant IL-2 immunotherapy and IL-2 gene therapy of i.p. growing murine plasmacytoma X63-Ag8.653. The kinetics of peritoneal exudate mononuclear cells were monitored during the progression and gene therapy of the plasmacytoma, using cytofluorometric analysis and monoclonal antibodies against T and NK cell subsets. It has been found that the percentage of mice protected against plasmacytoma transplants was higher in mice treated by transfer of genetically manipulated IL-2-producing plasmacytoma cells as compared to the mice repeatedly injected with recombinant IL-2. Intraperitoneal inoculation of the X63-Ag8.653 plasmacytoma led in most of the inoculated mice to an increased percentage of NK+, ASGM1+, Thy 1.2+, CD3+ and TCR alpha beta+ cells in the peritoneal fluid. The presence of macroscopically detectable i.p. tumours was accompanied by a higher increase in the percentage of NK+ and TCR gamma delta+ cells. Local IL-2 gene therapy of the plasmacytoma either prevented or diminished an increase in the percentage of CD3+, Thy 1.2+ and TCR alpha beta+ lymphocytes.

Animals↗