Santin A D, Ioli G R, Hiserodt J C, Manetta A, Pecorelli S, DiSaia P J, Granger G A
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717-3900, USA.
Am J Obstet Gynecol. 1996 Feb;174(2):633-40. doi: 10.1016/s0002-9378(96)70441-6.
We initiated studies to develop cytokine-secreting human ovarian carcinoma cells for the purpose of using these cells as vaccines for the treatment of advanced epithelial ovarian cancer.
A human ovarian carcinoma cell line (UCI-107) was genetically engineered to secrete the cytokine interleukin-2 by retroviral-mediated gene transduction.
One clone, termed UCI-107A IL-2 AS, constitutively secreted high levels of interleukin-2 (i.e., 2000 to 2300 pg/ml/10(5) cells per 48 hours) for > 55 passages and 8 months of study. Unlike parental- and vector-transduced cells, UCI-107A IL-2 AS cells were aneuploid and failed to express major histocompatibility complex class I and HER2/neu surface antigens. UCI-107A IL-2 AS cells were highly resistant to killing by gamma irradiation and continued to produce high levels of interleukin-2 even after irradiation with 10,000 cGy. Balb/C nude mice injected intraperitoneally with UCI 107-A IL-2 AS cells survived significantly longer than control animals, with 25% of the animals totally rejecting their tumors. UCI-107A IL-2 AS was totally resistant to killing by fresh allogeneic peripheral blood lymphocytes in four hour chromium 51 release assays but induced high levels of killing in 72-hour long-term cytotoxic assays.
The potential use of these interleukin-2-secreting ovarian carcinoma cells as vaccines for women with advance ovarian cancer will be discussed.
我们开展了相关研究，以培育能分泌细胞因子的人卵巢癌细胞，目的是将这些细胞用作治疗晚期上皮性卵巢癌的疫苗。
通过逆转录病毒介导的基因转导，对人卵巢癌细胞系（UCI-107）进行基因工程改造，使其分泌细胞因子白细胞介素-2。
一个名为UCI-107A IL-2 AS的克隆株在超过55代及8个月的研究期间持续分泌高水平的白细胞介素-2（即每48小时每10⁵个细胞分泌2000至2300 pg/ml）。与亲本细胞和载体转导细胞不同，UCI-107A IL-2 AS细胞为非整倍体，且不表达主要组织相容性复合体I类分子和HER2/neu表面抗原。UCI-107A IL-2 AS细胞对γ射线杀伤具有高度抗性，即使在接受10000 cGy照射后仍继续产生高水平的白细胞介素-2。腹腔注射UCI 107-A IL-2 AS细胞的Balb/C裸鼠存活时间明显长于对照动物，25%的动物完全排斥肿瘤。在4小时的⁵¹铬释放试验中，UCI-107A IL-2 AS对新鲜的同种异体外周血淋巴细胞杀伤完全耐受，但在72小时的长期细胞毒性试验中可诱导高水平的杀伤。
将讨论这些分泌白细胞介素-2的卵巢癌细胞作为晚期卵巢癌女性疫苗的潜在用途。
