Regression of bladder tumors in mice treated with interleukin 2 gene- modified tumor cells [published erratum appears in J Exp Med 1993 Jun 1;177(6):following 1831]
Regression of bladder tumors in mice treated with interleukin 2 gene- modified tumor cells [published erratum appears in J Exp Med 1993 Jun 1;177(6):following 1831]
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用白细胞介素 2 基因修饰的肿瘤细胞治疗的小鼠膀胱肿瘤的消退[发表的勘误表出现在 J Exp Med 1993 Jun 1;177(6):following 1831]
DOI：
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发表时间：
1993
影响因子：
15.3
通讯作者：
E. Gilboa
中科院分区：
文献类型：
--
作者：
J. Connor;R. Bannerji;S. Saito;W. Heston;W. Fair;E. Gilboa
本研究探讨了使用白细胞介素2（IL-2）和干扰素γ（IFN-γ）基因修饰的肿瘤细胞作为细胞疫苗治疗膀胱癌。所用的小鼠MBT-2肿瘤是人类膀胱癌的极好模型。这种致癌物诱导的膀胱来源肿瘤在病因学和组织学上与人类膀胱癌相似，并且以与其人类对应物相似的方式对治疗作出反应。使用逆转录病毒载体，将人IL-2和小鼠IFN-γ基因引入MBT-2细胞中并表达。细胞因子基因修饰的MBT-2细胞的肿瘤形成能力显著受损，因为在使用远远超过亲本MBT-2细胞的最小致瘤剂量的细胞剂量皮内注射IL-2-或IFN-γ-分泌细胞的小鼠中没有肿瘤形成。此外，排斥分泌IL-2或IFN-γ的肿瘤细胞的小鼠对随后用亲本MBT-2细胞进行的攻击具有高度抗性，但对38 C13细胞（一种具有相同遗传背景的B细胞淋巴瘤）没有抗性。为了使条件尽可能接近癌症患者中普遍存在的条件，使用灭活的分泌精氨酸的细胞来治疗携带通过将MBT-2细胞原位植入动物膀胱壁而建立的肿瘤的动物。用分泌IL-2的MBT-2细胞治疗携带显著肿瘤负荷的小鼠对肿瘤进展具有显著抑制作用，存活期延长。此外，在60%的小鼠中，肿瘤完全消退，并且动物在观察期间保持存活并且没有可检测的肿瘤。用分泌IL-2的MBT-2细胞治疗荷瘤动物上级使用顺铂（一种用于治疗膀胱癌的化疗剂）。IFN-γ分泌细胞的治疗效果是最小的，用未修饰的MBT-2细胞治疗对肿瘤生长或存活没有影响，表明亲本MBT-2细胞在该实验环境中是非免疫原性的。最重要的是，在用分泌IL-2的MBT-2细胞治疗后表现出完全肿瘤消退的小鼠变得对随后用高度致瘤剂量的亲本MBT-2细胞的攻击具有抗性，这表明在“治愈”的小鼠中建立了长期免疫记忆。
This study explored the use of interleukin 2 (IL-2) and interferon gamma (IFN-gamma) gene-modified tumor cells as cellular vaccines for the treatment of bladder cancer. The mouse MBT-2 tumor used is an excellent model for human bladder cancer. This carcinogen-induced tumor of bladder origin resembles human bladder cancer in its etiology and histology, and responds to treatment in a manner similar to its human counterpart. Using retroviral vectors, the human IL-2 and mouse IFN- gamma genes were introduced and expressed in MBT-2 cells. The tumor- forming capacity of the cytokine gene-modified MBT-2 cells was significantly impaired, since no tumors formed in mice injected intradermally with either IL-2- or IFN-gamma-secreting cells, using cell doses far exceeding the minimal tumorigenic dose of parental MBT-2 cells. Furthermore, mice that rejected the IL-2- or IFN-gamma-secreting tumor cells became highly resistant to a subsequent challenge with parental MBT-2 cells, but not to 38C13 cells, a B cell lymphoma of the same genetic background. To approximate the conditions as closely as possible to the conditions prevailing in the cancer patient, inactivated cytokine-secreting cells were used to treat animals bearing tumors established by orthotopic implantation of MBT-2 cells into the bladder wall of the animal. Treatment of mice carrying a significant tumor burden with IL-2-secreting MBT-2 cells had a significant inhibitory effect on tumor progression with extended survival. Moreover, in 60% of the mice the tumor regressed completely and the animals remained alive and free of detectable tumor for the duration of the observation period. Treatment of tumor-bearing animals with IL-2- secreting MBT-2 cells was superior to the use of cisplatin, a chemotherapeutic agent used in the treatment of bladder cancer. The therapeutic effect of IFN-gamma-secreting cells was minimal and treatment with unmodified MBT-2 cells had no effect on tumor growth or survival, showing that the parental MBT-2 cells were nonimmunogenic in this experimental setting. Most importantly, mice that exhibited complete tumor regression after treatment with IL-2-secreting MBT-2 cells became resistant to a subsequent challenge with a highly tumorigenic dose of parental MBT-2 cells, indicating that long-term immunological memory was established in the "cured" mice.
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影响因子：
11.2
作者：
I. Fidler
通讯作者：
I. Fidler
影响因子：
3.7
作者：
MARKOWITZ, D;GOFF, S;BANK, A
通讯作者：
BANK, A
白细胞介素 2 在癌症治疗中的潜在用途。
影响因子：
2.8
作者：
Cheever,MA;Thompson,JA;Peace,DJ;Greenberg,PD
通讯作者：
Greenberg,PD
细胞介导的淋巴溶解 (CML) 测定中培养的 T 细胞的功能和抗原特性。
影响因子：
2.7
作者：
Zier,KS
通讯作者：
Zier,KS