van Leeuwen E B M, Cloosen S, Senden-Gijsbers B L M G, Agervig Tarp M, Mandel U, Clausen H, Havenga M J E, Duffour M-T, García-Vallejo J J, Germeraad W T V, Bos G M J
Department of Internal Medicine, Division of Hemato-Oncology, University Hospital Maastricht, Maastricht, The Netherlands.
Cytotherapy. 2006;8(1):24-35. doi: 10.1080/14653240500513018.
DC-presenting tumor Ag are currently being developed to be used as a vaccine in human cancer immunotherapy. To increase chances for successful therapy it is important to deliver full-length tumor Ag instead of loading single peptides.
In this study we used a fiber-modified adenoviral vector (rAd5F35) containing full-length tumor Ag cDNA to transduce human monocyte (Mo)-derived DC in vitro. Cells were efficiently transduced and survived for at least 3 days after adenoviral transduction. Phenotype and function after maturation of Mo-DC were not impaired by infection with adenovirus particles. Expression of the tumor-associated Ag mucin-1 (MUC1) was detected using MAb defining different MUC1 glycoforms.
Non-transduced mature Mo-DC express endogenous MUC1 with normal glycosylation. After transduction with the rAd5F35-MUC1 adenoviral vector, Mo-DC also expressed MUC1 with tumor-associated glycosylation (Tn and T glycoforms), although no changes in mRNA levels of relevant glycosyltransferases could be demonstrated.
The presence of aberrantly glycosylated MUC1 may influence Ag presentation of the tumor glycoforms of MUC1 to immune cells, affecting tumor cell killing. These findings could be highly relevant to developing strategies for cancer immunotherapy based on DC vaccines using MUC1 as tumor Ag.
目前正在研发将呈递肿瘤抗原的树突状细胞（DC）用作人类癌症免疫疗法中的疫苗。为提高成功治疗的几率，递送全长肿瘤抗原而非加载单个肽段很重要。
在本研究中，我们使用一种包含全长肿瘤抗原cDNA的纤维修饰腺病毒载体（rAd5F35）在体外转导人单核细胞（Mo）来源的DC。腺病毒转导后，细胞被有效转导并存活至少3天。腺病毒颗粒感染未损害Mo-DC成熟后的表型和功能。使用定义不同MUC1糖型的单克隆抗体检测肿瘤相关抗原粘蛋白-1（MUC1）的表达。
未转导的成熟Mo-DC表达具有正常糖基化的内源性MUC1。用rAd5F-35-MUC1腺病毒载体转导后，Mo-DC也表达具有肿瘤相关糖基化（Tn和T糖型）的MUC1，尽管相关糖基转移酶的mRNA水平未显示出变化。
异常糖基化的MUC1的存在可能会影响MUC1肿瘤糖型向免疫细胞的抗原呈递，从而影响肿瘤细胞的杀伤。这些发现可能与基于使用MUC1作为肿瘤抗原的DC疫苗制定癌症免疫治疗策略高度相关。
