投递途径、MyD88 信号和交叉引发事件决定了基于腺病毒的黑色素瘤疫苗的抗肿瘤疗效。
Delivery route, MyD88 signaling and cross-priming events determine the anti-tumor efficacy of an adenovirus based melanoma vaccine.
机构信息
Department of Medical Oncology, VU University Medical Center and Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
出版信息
Vaccine. 2011 Mar 9;29(12):2313-21. doi: 10.1016/j.vaccine.2011.01.022. Epub 2011 Jan 25.
Abstract
Adenovirus (Ad)-based vaccines are considered for cancer immunotherapy, yet, detailed knowledge on their mechanism of action and optimal delivery route for anti-tumor efficacy is lacking. Here, we compared the anti-tumor efficacy of an Ad-based melanoma vaccine after intradermal, intravenous, intranasal or intraperitoneal delivery in the B16F10 melanoma model. The intradermal route induced superior systemic anti-melanoma immunity which was MyD88 signaling-dependent. Predominant transduction of non-professional antigen-presenting cells at the dermal vaccination sites and draining lymph nodes, suggested a role for cross-presentation, which was confirmed in vitro. We conclude that the dermis provides an optimal route of entry for Ad-based vaccines for high-efficacy systemic anti-tumor immunization and that this immunization likely involves cross-priming events in the draining lymph nodes.
摘要
腺病毒（Ad）疫苗被认为可用于癌症免疫治疗，但对于其作用机制和最佳给药途径以实现抗肿瘤疗效的详细了解仍有所欠缺。在这里，我们比较了在 B16F10 黑色素瘤模型中经皮内、静脉内、鼻内或腹腔内给药后基于腺病毒的黑色素瘤疫苗的抗肿瘤疗效。皮内途径诱导了更优的全身性抗黑色素瘤免疫，该免疫依赖于 MyD88 信号。在皮肤接种部位和引流淋巴结中，主要转导非专业抗原呈递细胞，提示存在交叉呈递作用，这在体外得到了证实。我们得出结论，真皮为基于腺病毒的疫苗提供了进入机体的最佳途径，以实现高效的全身性抗肿瘤免疫，并且这种免疫可能涉及引流淋巴结中的交叉引发事件。
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