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Genes encoding the p35 and p40 subunits of human interleukin-12 (IL-12) and the bacterial aminoglycoside phosphotransferase were cloned into a mammalian expression plasmid. The resultant plasmid, pCMVIL-12neo, was used to transfect human lung tumor cell lines in vitro. Stably transfected subclones were generated and found to secrete human IL-12 for at least 10 days following a lethal dose of gamma-radiation. The ability of the IL-12--producing tumor cells to promote an antitumor response in vivo was evaluated in SCID mice co-engrafted subcutaneously with human peripheral blood lymphocytes (PBLs) and viable human lung tumor cells (SCID-Winn assay). Using this model system, it was established that IL-12 released locally into tumors by irradiated IL-12--transfected cells activated the human PBL and promoted their ability to suppress tumor development in a dose-dependent fashion. PBL subset depletion studies revealed that the antitumor effect promoted by the IL-12--modified cells was dependent on the presence of human CD8(+) T cells and, to a lesser extent, human CD56(+) natural killer cells within the xenograft. We conclude that (a) irradiated human lung tumor cells genetically modified with pCMVIL-12neo secrete bioactive human IL-12 at concentrations sufficient to promote a human lymphocyte-mediated antitumor response in the microenvironment of the xenograft, and (b) that the SCID-Winn assay provides a useful model for the preclinical evaluation of cytokine-based human immunotherapy protocols.

A 28-year-old Japanese man was admitted to our institute because of sharp anal pain and a mass that prolapsed from the anus after defecation. After spinal anesthesia for emergency operation, the mass spontaneously withdrew into the anus and the pain disappeared. Surgery was postponed. Barium enema and colonoscopy revealed a pedunculated polyp in the sigmoid colon, which was removed by snare polypectomy with electrocautery. The resected polyp was granular and reddish, and measured 33 x 22 x 14 mm. Histological examination of the polyp revealed a cavernous hemangioma. Hemangioma of the colon is rare; only 52 cases have been reported in Japan. Of these patients, eight underwent endoscopic polypectomy. The present lesion is the largest thus treated that has been documented. Endoscopic polypectomy seems to be a safe and preferable procedure for the diagnosis and treatment of small, solitary polypoid hemangiomas of the colon.