Delivery of Interferon-α Transfected Dendritic Cells into Central Nervous System Tumors Enhances the Antitumor Efficacy of Peripheral Peptide-Based Vaccines
Delivery of Interferon-α Transfected Dendritic Cells into Central Nervous System Tumors Enhances the Antitumor Efficacy of Peripheral Peptide-Based Vaccines
复制标题
将干扰素-α转染的树突状细胞递送至中枢神经系统肿瘤中可增强外周肽疫苗的抗肿瘤功效
作者：
H. Okada;T. Tsugawa;Hidemitsu Sato;N. Kuwashima;A. Gambotto;K. Okada;Jill E. Dusak;W. Fellows;G. Papworth;Simon C Watkins;W. Chambers;D. Potter;W. Storkus;I. Pollack
我们评估了将干扰素（IFN）-α转染的树突状细胞（DC-IFN-α）注射到小鼠颅内肿瘤中对免疫和存活的影响，所述小鼠预先用卵白蛋白衍生的CTL或T辅助表位致敏的同基因树突状细胞（DC）免疫。这些免疫保护动物免受皮下感染。用表达卵清蛋白的M05黑色素瘤（I类+和II类阴性）攻击。值得注意的是，在用卵清蛋白衍生的T辅助表位接种的动物中观察到抗卵清蛋白CTL应答，但仅在用M05细胞攻击小鼠之后。这种CTL的交叉致敏依赖于CD 4+和CD 8 + T细胞。因为我们观察到南卡罗来纳州，而非颅内，肿瘤被CD 11 c + DC浸润，并且由于IFN-α促进DC和T细胞的活化和存活，我们评估了将腺病毒（Ad）-IFN-α-工程化DC注射到预先免疫小鼠的颅内M05肿瘤中的组合抗肿瘤作用。递送DC-IFN-α延长存活。这对于用CTL和T辅助卵清蛋白表位预接种的动物是最显著的，其中60%（10只中的6只）的小鼠（相对于10只对照动物中的0只）在肿瘤攻击后存活>80天。DC-IFN-α似乎比模拟转染的DC在颅内肿瘤微环境中持续更长时间，并且DC-IFN-α处理的小鼠在引流颈淋巴结中表现出卵清蛋白特异性CTL水平的增强。基于这些结果，我们认为颅内肿瘤部位DC局部表达IFN-α可能会增强脑肿瘤外周疫苗方法的临床疗效。
We evaluated the effects, on immunity and survival, of injection of interferon (IFN)-α-transfected dendritic cells (DC-IFN-α) into intracranial tumors in mice immunized previously with syngeneic dendritic cells (DCs) pulsed either with ovalbumin-derived CTL or T helper epitopes. These immunizations protected animals from s.c. challenge with ovalbumin-expressing M05 melanoma (class I+ and class II-negative). Notably, antiovalbumin CTL responses were observed in animals vaccinated with an ovalbumin-derived T helper epitope but only after the mice were challenged with M05 cells. This cross-priming of CTL was dependent on both CD4+ and CD8+ T cells. Because we observed that s.c., but not intracranial, tumors were infiltrated with CD11c+ DCs, and because IFN-α promotes the activation and survival of both DCs and T cells, we evaluated the combinational antitumor effects of injecting adenoviral (Ad)-IFN-α-engineered DCs into intracranial M05 tumors in preimmunized mice. Delivery of DC-IFN-α prolonged survival. This was most notable for animals prevaccinated with both the CTL and T helper ovalbumin epitopes, with 60% (6 of 10) of mice (versus 0 of 10 of control animals) surviving for >80 days after tumor challenge. DC-IFN-α appeared to persist longer than mock-transfected DCs within the intracranial tumor microenvironment, and DC-IFN-α-treated mice exhibited enhanced levels of ovalbumin-specific CTL in draining cervical lymph nodes. On the basis of these results, we believe that local expression of IFN-α by DCs within the intracranial tumor site may enhance the clinical efficacy of peripheral vaccine approaches for brain tumors.
生物调节剂成功治疗黑色素瘤患者的中枢神经系统复发。
DOI：
10.1200/jco.1989.7.11.1701
发表时间：
1989
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Mitchell,MS
通讯作者：
Mitchell,MS
影响因子：
4.4
作者：
J. Kao;Y. Gong;Chuan-min Chen;Qiong-duan Zheng;Jian-Jun Chen
通讯作者：
J. Kao;Y. Gong;Chuan-min Chen;Qiong-duan Zheng;Jian-Jun Chen