Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells

作者: J Connor , R Bannerji , S Saito , W Heston , W Fair

DOI: 10.1084/JEM.177.4.1127

关键词: Interleukin 2BiologyPathologyCancer stem cellLymphokine-activated killer cellCytokineCarcinogenesisTumor progressionBladder cancerAdoptive cell transfer

摘要: This study explored the use of interleukin 2 (IL-2) and interferon gamma (IFN-gamma) gene-modified tumor cells as cellular vaccines for treatment bladder cancer. The mouse MBT-2 used is an excellent model human carcinogen-induced origin resembles cancer in its etiology histology, responds to a manner similar counterpart. Using retroviral vectors, IL-2 IFN-gamma genes were introduced expressed cells. tumor-forming capacity cytokine was significantly impaired, since no tumors formed mice injected intradermally with either IL-2- or IFN-gamma-secreting cells, using cell doses far exceeding minimal tumorigenic dose parental Furthermore, that rejected became highly resistant subsequent challenge but not 38C13 B lymphoma same genetic background. To approximate conditions closely possible prevailing patient, inactivated cytokine-secreting treat animals bearing established by orthotopic implantation into wall animal. Treatment carrying significant burden IL-2-secreting had inhibitory effect on progression extended survival. Moreover, 60% regressed completely remained alive free detectable duration observation period. tumor-bearing superior cisplatin, chemotherapeutic agent therapeutic unmodified growth survival, showing nonimmunogenic this experimental setting. Most importantly, exhibited complete regression after indicating long-term immunological memory "cured" mice.

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