INTERLEUKIN-2 GENE-THERAPY OF SURGICAL MINIMAL RESIDUAL TUMOR DISEASE

Our study was designed to examine the effects of IL-2 gene therapy in a surgical minimal residual tumour disease (SMRTD), Mice were inoculat ed 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 SMRT D''), On day 90 after surgery, the tumour recurrence rate in untreated mice with microscopic SMRTD was approximately 30%, whereas in those w ith macroscopic SMRTD it was 75%, After surgery, experimental mice wer e treated with 2 types of irradiated, IL-2 gene-modified, IL-2-produci ng tumour cell vaccine, One type of vaccine was derived from the MC12 sarcoma cells (MC12-IL2/IV-3); the other type was derived from an unre lated X63-Ag8.653 plasmacytoma (X63-m-IL-2), Both types of vaccine fai led 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 w as capable of preventing growth in all but one mouse (1/64) with micro scopic SMRTD when administered 2 to 5 days after surgery, If the vacci nation took place 2 days before surgery or later than 5 days after sur gery, the therapeutic activity was lost, Vaccination with irradiated p arental MC12 cells did not produce any significant benefit compared to the operated-only mice. The protective effect of the MC12-IL2/IV-3 va ccine was specific and comparatively long-lasting, Vaccinated mice, wh ich 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. (C) 1998 Wiley- Liss, Inc.