GENE-THERAPY OF CANCER - USE OF IL-2 GENE-TRANSFER AND KINETICS OF LOCAL T-CELL 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 againstplasmacytoma 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 TCRalphabeta+ 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 TCRgammadelta+ cells. Local IL-2 gene therapy of the plasmacytoma either prevented or diminished an increase in the percentage of CD3+, Thy 1.2+ and TCRalphabeta+ lymphocytes.