Fluorine-modified sialyl-Tn-CRM197 vaccine elicits a robust immune response
Fluorine-modified sialyl-Tn-CRM197 vaccine elicits a robust immune response
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氟修饰唾液酸-Tn-CRM197 疫苗可引发强大的免疫反应
DOI：
10.1007/s10719-019-09884-0
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发表时间：
2019-10-01
影响因子：
3
通讯作者：
Zhou, Yifa
中科院分区：
文献类型：
--
作者：
Song, Chengcheng;Zheng, Xiu-Jing;Zhou, Yifa
尽管靶向上皮癌细胞上的肿瘤相关碳水化合物抗原的疫苗呈现出有吸引力的治疗方法，但相对较差的免疫原性限制了其发展。在这项研究中，我们研究了氟取代的唾液酸-Tn（F-STn）类似物耦合到白喉毒素197（CRM 197）的无毒交叉反应材料的免疫活性。我们的结果表明，F-STn-CRM 197比非氟化STn-CRM 197促进更大的免疫原性。在存在或不存在佐剂的情况下，F-STn-CRM 197通过增加抗原特异性淋巴细胞增殖和诱导混合Th 1/Th 2应答，导致IFN-γ和IL-4细胞因子以及STn特异性抗体的产生，显著增强针对STn的细胞和体液免疫。此外，由F-STn-CRM 197免疫产生的抗血清显著识别STn阳性肿瘤细胞，并增加由抗体依赖性细胞介导的细胞毒性（ADCC）或补体依赖性细胞毒性（CDC）途径诱导的癌细胞溶解。我们的数据表明，这种F-STn疫苗可能用于癌症免疫治疗，并可能用于预防性预防癌症。
Even though a vaccine that targets tumor-associated carbohydrate antigens on epithelial carcinoma cells presents an attractive therapeutic approach, relatively poor immunogenicity limits its development. In this study, we investigated the immunological activity of a fluoro-substituted Sialyl-Tn (F-STn) analogue coupled to the non-toxic cross-reactive material of diphtheria toxin197 (CRM197). Our results indicate that F-STn-CRM197 promotes a greater immunogenicity than non-fluorinated STn-CRM197. In the presence or absence of adjuvant, F-STn-CRM197 remarkably enhances both cellular and humoral immunity against STn by increasing antigen-specific lymphocyte proliferation and inducing a mixed Th1/Th2 response leading to production of IFN-γ and IL-4 cytokines, as well as STn-specific antibodies. Furthermore, antisera produced from F-STn-CRM197 immunization significantly recognizes STn-positive tumor cells and increases cancer cell lysis induced by antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) pathways. Our data suggest that this F-STn vaccine may be useful for cancer immunotherapy and possibly for prophylactic prevention of cancer.