Antitumoral vaccination with granulocyte-macrophage colony-stimulating factor or interleukin-12-expressing DHD/K12 colon adenocarcinoma cells

Immunomodulating gene therapy for the treatment of malignant diseases is un der extensive investigation. In this study, we induced an antitumoral immun e response with murine interleukin-12 (mIL-12) and murine granulocyte-macro phage colony-stimulating factor (GM-CSF)-secreting tumor cells in a model o f peritoneal carcinomatosis. Intraperitoneal injection of DHD/K12 tumoral c ells engineered to produce IL-12 or GM-CSF did not generate any tumors, whe reas untransduced DHD/K12 cells gave rise to peritoneal carcinomatosis. IL- 12-expressing DHD/K12 cells also protected against tumors derived from coin jected parental cells. To test whether cytokine-producing cells could elici t a memory antitumoral immune response, animals received a challenge with p arental DHD/K12 cells 35 days after the injection of proliferating or irrad iated DHD/K12 engineered cells. Under our experimental conditions, irradiat ed tumor cells did not generate any antitumoral immunity. In contrast tumor development was delayed and survival increased in the animals vaccinated w ith cytokine-secreting proliferating cells. A specific cytotoxic T-lymphocy te response against DHD/K12 parental cells was observed after vaccination w ith CM-CSF-expressing cells. Our results demonstrated that intraperitoneal vaccination with IL-12- or CM-CSF-expressing adenocarcinoma cells induced a systemic immune antitumoral response that may be useful as an adjuvant the rapy after surgical resection of colorectal cancer.