Interleukin‐2 gene therapy of surgical minimal residual tumour disease

• Published in: International journal of cancer 1998-03, Vol.76 (1), p.115-119
• Main Authors: Vlk, V., Rössner, P., Indrová, M., Bubeník, J., Sobota, V.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Genetic Therapy; Immunologic Memory; Interleukin-2 - genetics; Lymphocyte Count; Lymphocyte Subsets; Medical sciences; Methylcholanthrene; Mice; Mice, Inbred C57BL; Neoplasm, Residual - surgery; Neoplasm, Residual - therapy; Other treatments; Sarcoma, Experimental - chemically induced; Sarcoma, Experimental - therapy; Transfection; Treatment. General aspects; Tumors; Vaccination
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19980330)76:1<115::AID-IJC18>3.0.CO;2-B

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‐IL2/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 (1/64) 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‐IL2/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. Int. J. Cancer 76:115–119, 1998.© 1998 Wiley‐Liss, Inc.