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肿瘤内树突状细胞疫苗接种可引发大鼠对恶性胶质瘤的强效杀瘤免疫。

Intratumoral dendritic cell vaccination elicits potent tumoricidal immunity against malignant glioma in rats.

作者信息

Ehtesham Moneeb, Kabos Peter, Gutierrez Mervin A R, Samoto Ken, Black Keith L, Yu John S

机构信息

Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

出版信息

J Immunother. 2003 Mar-Apr;26(2):107-16. doi: 10.1097/00002371-200303000-00003.

Abstract

Dendritic cells (DC) are attractive candidates for innovative cancer immunotherapy by virtue of their ability to function as powerful antigen presenting cells and elicit potent antitumor cytotoxic immune responses. With the aim of generating antitumor immunity, the authors sought to enhance in vivo tumor antigen presentation by using an intratumoral DC vaccination strategy in the setting of partially irradiated intracranial brain tumors. Fisher rats, implanted with 9L gliomas in the right corpus striatum, were treated with freshly cultured, unpulsed syngeneic DC inoculated directly into the tumor bed. Intracranially inoculated DCs were found to drain to ipsilateral deep cervical lymph nodes. This was associated with increased local and systemic antitumor cytoxicity, as evidenced by robust infiltration of treated tumors with CD4 and CD8 T cells as well as by increased IFN-gamma protein and message levels in in vitro restimulated splenic lymphocytes. DC therapy resulted in prolonged survival and immunity to subsequent intracranial tumor re-challenge. These results demonstrate the viability of intratumoral DC vaccination as an effective therapeutic strategy for intracranial glioma.

摘要

树突状细胞(DC)凭借其作为强大抗原呈递细胞的功能以及引发有效的抗肿瘤细胞毒性免疫反应的能力,成为创新型癌症免疫疗法的有吸引力的候选者。为了产生抗肿瘤免疫力,作者试图通过在部分照射的颅内脑肿瘤背景下使用瘤内DC疫苗接种策略来增强体内肿瘤抗原呈递。将9L胶质瘤植入右侧纹状体的Fisher大鼠,用新鲜培养的、未脉冲处理的同基因DC直接接种到肿瘤床进行治疗。发现颅内接种的DC引流至同侧颈深淋巴结。这与局部和全身抗肿瘤细胞毒性增加有关,表现为治疗的肿瘤中有大量CD4和CD8 T细胞浸润,以及体外再刺激的脾淋巴细胞中IFN-γ蛋白和信息水平增加。DC疗法导致生存期延长,并对随后的颅内肿瘤再次攻击产生免疫。这些结果证明了瘤内DC疫苗接种作为颅内胶质瘤有效治疗策略的可行性。

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