[en] Immunomodulating gene therapy for the treatment of malignant diseases is under extensive investigation. In this study, we induced an antitumoral immune response with murine interleukin-12 (mIL-12) and murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor cells in a model of peritoneal carcinomatosis. Intraperitoneal injection of DHD/K12 tumoral cells engineered to produce IL-12 or GM-CSF did not generate any tumors, whereas untransduced DHD/K12 cells gave rise to peritoneal carcinomatosis. IL-12-expressing DHD/K12 cells also protected against tumors derived from coinjected parental cells. To test whether cytokine-producing cells could elicit a memory antitumoral immune response, animals received a challenge with parental DHD/K12 cells 35 days after the injection of proliferating or irradiated DHD/K12 engineered cells. Under our experimental conditions, irradiated tumor cells did not generate any antitumoral immunity. In contrast, tumor development was delayed and survival increased in the animals vaccinated with cytokine-secreting proliferating cells. A specific cytotoxic T-lymphocyte response against DHD/K12 parental cells was observed after vaccination with GM-CSF-expressing cells. Our results demonstrated that intraperitoneal vaccination with IL-12- or GM-CSF-expressing adenocarcinoma cells induced a systemic immune antitumoral response that may be useful as an adjuvant therapy after surgical resection of colorectal cancer.
Disciplines :
Oncology
Author, co-author :
Lechanteur, Chantal ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Moutschen, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Princen, Frederic
Lopez, Marie-Josée ; Université de Liège - ULiège > Département des sciences cognitives > Département des sciences cognitives
Franzen, E.
Gielen, Jacques
Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine
Merville, Marie-Paule ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Language :
English
Title :
Antitumoral Vaccination with Granulocyte-Macrophage Colony-Stimulating Factor or Interleukin-12-Expressing Dhd/K12 Colon Adenocarcinoma Cells
Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA. 1993;90:3539-3543.
Amstrong CA, Botella R, Galloway TH, et al. Antitumor effects of granulocyte-macrophage colony-stimulating factor production by melanoma cells. Cancer Res. 1996;56: 2191-2198.
Lee C-T, Wu S, Ciernik F, et al. Genetic immunotherapy of established tumors with adenovirus-murine granulocyte-macrophage colony-stimulating factor. Hum Gene Ther. 1997;8:187-193.
Pardoll DM. Paracrine cytokine adjuvants in cancer immunotherapy. Annu Rev Immunol. 1995;13:399-415.
Inaba K, Inaba M, Romani N, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992;176:1693-1702.
Larsen CP, Ritchie SC, Hendrix R, et al. Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dendritic cells. J Immunol. 1994;152:5208-5219.
Colombo MP, Ferrari G, Stoppacciaro A, et al. Granulocyte colony-stimulating factor gene transfer suppresses tumorigenicity of a murine adenocarcinoma in vivo. J Exp Med. 1991;173:889-897.
Yoshida H, Enomoto H, Tagawa M, et al. Impaired tumorigenicity and decreased liver metastasis of murine neuroblastoma cells engineered to secrete interleukin-2 or granulocyte-macrophage colony-stimulating factor. Cancer Gene Ther. 1998;5:67-73.
Aruga E, Aruga A, Area MJ, et al. Immune responsiveness to a murine mammary carcinoma modified to express B7-1, interleukin-12, or GM-CSF. Cancer Gene Ther. 1997;4:157-166.
Yu JS, Burwick JA, Dranoff G, et al. Gene therapy for metastatic brain tumors by vaccination with granulocyte-macrophage colony-stimulating factor-transduced tumor cells. Hum Gene Ther. 1997;8:1065-1072.
Mahvi DM, Burkholder JK, Turner J, et al. Particle-mediated gene transfer of granulocyte-macrophage colony-stimulating factor cDNA to tumor cells: Implications for a clinically relevant tumor vaccine. Hum Gene Ther. 1996;7:1535-1543.
Robertson MJ, Ritz J. Interleukin 12: basic biology and potential applications in cancer treatment. Oncologist. 1996;1:88-97.
Tahara H, Lotze MT. Antitumor effects of interleukin-12 (IL-12): applications for the immunotherapy and gene therapy of cancer. Gene Ther. 1995;2:96-106.
Wolf SF, Sieburth D, Sypek J. Interleukin 12: a key modulator of immune function. Stem Cells. 1994;12:154-168.
Lode HN, Dreier T, Xiang R, et al. Gene therapy with a single chain interleukin 12 fusion protein induces T cell-dependent protective immunity in a syngeneic model of murine neuroblastoma. Proc Natl Acad Sci USA. 1998;95: 2475-2480.
Tahara H, Zitvogel L, Storkus WJ, et al. Effective eradication of established murine tumors with IL-12 gene therapy using a polycistronic retroviral vector. J Immunol. 1995;154:6466-6474.
Colombo MP, Vagliani M, Spreafico F, et al. Amount of interleukin-12 available at the tumor site is critical for tumor regression. Cancer Res. 1996;56:2531-2534.
Sumimoto H, Tani K, Nakazaki Y, et al. Superiority of IL-12-transduced murine lung cancer cells to GM-CSF or B7-1 (CD80) transfectants for therapeutic antitumor immunity in syngeneic immunocompetent mice. Cancer Gene Ther. 1998;5:29-37.
Perrin P, Cassagnau E, Burg C, et al. An interleukin 2/sodium butyrate combination as immunotherapy for rat colon cancer peritoneal carcinomatosis. Gastroenterology. 1994;107:1697-1708.
Patry Y, Douillard J-Y, Meflah K, et al. Immunization against a rat colon carcinoma by sodium butyrate-treated cells but not by interleukin 2-secreting cells. Gastroenterology. 1995;109:1555-1565.
Dearden-Badet M-J, Pelletier H, Caignard A, et al. In vitro proliferative responses of spleen lymphocytes from rats bearing progressive or regressive tumors induced by cell variants of a syngeneic colon carcinoma. Int J Cancer. 1989;43:334-339.
Caignard A, Pelletier H, Martin F. Specificity of the immune response leading to protection or enhancement by regressive and progressive variants of a rat colon carcinoma. Int J Cancer. 1988;42:883-886.
Forrest SM, Ng KW, Findlay DM, et al. Characterization of an osteoblast-like clonal cell line which responds to both parathyroid hormone and calcitonin. Calcif Tissue Int. 1985;37:51-56.
Partridge NC, Alcorn D, Michelangeli VP, et al. Morphological and biochemical characterization of four clonal osteogenic sarcoma cell lines of rat origin. Cancer Res. 1983;43:4308-4314.
Lechanteur C, Princen F, Lo Bue S, et al. HSV-1 thymidine kinase gene therapy for colorectal adenocarcinoma-derived peritoneal carcinomatosis. Gene Ther. 1997;4:1189-1194.
Cosset F-L, Takeuchi Y, Battini J-L, et al. High-liter packaging cells producing recombinant retroviruses resistant to human serum. J Virol. 1995;69:7430-7436.
Coughlin CM, Salhany KE, Wysocka M, et al. Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest. 1998;101:1441-1452.
Koo J, Fung K, Siu KF. Recovery of malignant tumor cells from the right atrium during hepatic resection for hepatocellular carcinoma. Cancer. 1983;52:1952-1956.
Salsbury AJ, McKinna JA, Griffiths JP. Circulating cancer cells during excision of carcinomas of the rectum and colon with high ligation of the inferior mesenteric vein. Surg Gynecol Obstet. 1965;120:1266-1270.
Liefers G-J, Cleton-Jansen A-M, Van de Velde CJH, et al. Micrometastases and survival in stage II colorectal cancer. N Engl J Med. 1998;339:223-228.
Lennard TW, Shenton BK, Borzotta A. The influence of surgical operations on components of the human immune system. Br J Surg. 1985;72:771-776.
Pirenne J, Ribbens C, Médot M, et al. Adverse effects of abdominal operations on production of interferon γ. Eur J Surg. 1995;161:77-83.
Slade NS, Simmons RL, Yunis E. Immunodepression after major surgery in normal patients. Surgery. 1975;78:363-372.