Chondronasiou Dafni, Eisden Tracy-Jane T H D, Stam Anita G M, Matthews Qiana L, Icyuz Mert, Hooijberg Erik, Dmitriev Igor, Curiel David T, de Gruijl Tanja D, van de Ven Rieneke
Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.
Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, The Netherlands.
Vaccines (Basel). 2018 Jul 18;6(3):42. doi: 10.3390/vaccines6030042.
To mount a strong anti-tumor immune response, non T cell inflamed (cold) tumors may require combination treatment encompassing vaccine strategies preceding checkpoint inhibition. In vivo targeted delivery of tumor-associated antigens (TAA) to dendritic cells (DCs), relying on the natural functions of primary DCs in situ, represents an attractive vaccination strategy. In this study we made use of a full-length MART-1 expressing C/B-chimeric adenoviral vector, consisting of the Ad5 capsid and the Ad3 knob (Ad5/3), which we previously showed to selectively transduce DCs in human skin and lymph nodes. Our data demonstrate that chimeric Ad5/3 vectors encoding TAA, and able to target human DCs in situ, can be used to efficiently induce expansion of functional tumor-specific CD8⁺ effector T cells, either from a naïve T cell pool or from previously primed T cells residing in the melanoma-draining sentinel lymph nodes (SLN). These data support the use of Ad3-knob containing viruses as vaccine vehicles for in vivo delivery. "Off-the-shelf" DC-targeted Ad vaccines encoding TAA could clearly benefit future immunotherapeutic approaches.
为了引发强大的抗肿瘤免疫反应，非T细胞炎症性（冷）肿瘤可能需要包括在检查点抑制之前采用疫苗策略的联合治疗。依靠原位初级树突状细胞（DC）的自然功能，将肿瘤相关抗原（TAA）体内靶向递送至DC，是一种有吸引力的疫苗接种策略。在本研究中，我们使用了一种表达全长MART-1的C/B嵌合腺病毒载体，其由Ad5衣壳和Ad3纤突组成（Ad5/3），我们之前证明该载体可在人皮肤和淋巴结中选择性转导DC。我们的数据表明，编码TAA且能够原位靶向人DC的嵌合Ad5/3载体，可用于有效诱导功能性肿瘤特异性CD8⁺效应T细胞的扩增，无论是来自初始T细胞库还是来自存在于黑色素瘤引流前哨淋巴结（SLN）中的先前致敏T细胞。这些数据支持使用含Ad3纤突的病毒作为体内递送的疫苗载体。编码TAA的“现成”DC靶向Ad疫苗显然将有益于未来的免疫治疗方法。
