Interleukin-2 gene therapy of surgical minimal residual tumour disease.
Our study was designed to examine the effects of IL-2 gene therapy in a surgical minimal residual tumour disease (SMRTD). Mice were inoculated s.c. with methylcholanthrene (MC)-induced MC12 sarcoma cells. When the tumours reached 8 to 12 mm in diameter, they were excised, either completely ("microscopic SMRTD") or incompletely ("macroscopic SMRTD"). On day 90 after surgery, the tumour recurrence rate in untreated mice with microscopic SMRTD was approximately 30%, whereas in those with macroscopic SMRTD it was 75%. After surgery, experimental mice were treated with 2 types of irradiated, IL-2 gene-modified, IL-2-producing tumour cell vaccine. One type of vaccine was derived from the MC12 sarcoma cells (MC12-1L2/IV-3); the other type was derived from an unrelated X63-Ag8.653 plasmacytoma (X63-m-IL-2). Both types of vaccine failed to cure the macroscopic SMRTD. Whereas the X63-m-IL-2 vaccine was also ineffective in the microscopic SMRTD, the MC12-IL2/IV-3 vaccine was capable of preventing growth in all but one mouse (1164) with microscopic SMRTD when administered 2 to 5 days after surgery. If the vaccination took place 2 days before surgery or later than 5 days after surgery, the therapeutic activity was lost. Vaccination with irradiated parental MC12 cells did not produce any significant benefit compared to the operated-only mice. The protective effect of the MC12-L2/IV-3 vaccine was specific and comparatively long-lasting. Vaccinated mice, which had rejected the MC12 tumour residuum, were capable of rejecting a second inoculum of the MC12 sarcoma cells injected on days 35 to 110 after surgery but succumbed to the growth of 2 other unrelated murine sarcomas carrying different tumour-rejection antigens.
Vlk
V
V
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Second Faculty of Medicine, Charles University, Prague.
Rössner
P
P
Indrová
M
M
Bubeník
J
J
Sobota
V
V
D000818:Animals; D015316:Genetic Therapy; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000235:genetics*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008748:Methylcholanthrene; D051379:Mice; D008810:Mice, Inbred C57BL; D018365:Neoplasm, Residual / Q000601:surgery / Q000628:therapy*; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000628:therapy*; D014162:Transfection; D014611:Vaccination
D007376:Interleukin-2; D008748:Methylcholanthrene