Interleukin 2 gene therapy of residual disease in mice carrying tumours induced by HPV 16

Experiments were designed to examine the efficacy of IL-2 gene therapy in a surgical minimal residual tumour disease, using moderately immunogenic MK1 6/1/IIIABC murine cells transformed by activated ras and HPV 16 E6/E7 oncog enes (MK16 cells). Previously we demonstrated that surgical minimal residua l tumour disease (SMRTD) could be effectively cured when murine Mc12 sarcom a had been resected and the operated mice were treated with irradiated Mc12 sarcoma cells engineered to secrete IL-2. In this study we performed IL-2 gene therapy of MK16 carcinoma with two types of irradiated MK16-unrelated tumour cell vaccines. One type of vaccine was derived from MHC class I-matc hed Mc12 sarcoma cells engineered to secrete IL-2 and the other from MHC cl ass I-discordant IL-2 producing plasmacytoma X63-m-IL-2. The vaccines did n ot share any tumour rejection antigen with the MK16 cells and served exclus ively as a local source of IL-2 production. Both vaccines were capable of i nhibiting MK16 tumours when administered peritumorally up to 15 days after MK16 tumour challenge. The irradiated MHC class I-matched and IL-2-producin g Mc12 sarcoma vaccine was then selected for therapy of MK16 SMRTD. Whereas the recurrence rate in the operated MK16 carcinoma bearers was 80%, so tha t only 20% of mice were cured by surgery, approximately 65% of the MK16 car cinoma bearers were permanently protected when the surgery was followed by local administration of the IL-2-producing Mc12 sarcoma vaccine.