A novel cancer immunotherapy based on the combination of a synthetic carbohydrate-pulsed dendritic cell vaccine and glycoengineered cancer cells.
A novel cancer immunotherapy based on the combination of a synthetic carbohydrate-pulsed dendritic cell vaccine and glycoengineered cancer cells.
复制标题
一种基于合成碳水化合物脉冲树突状细胞疫苗和糖工程癌细胞组合的新型癌症免疫疗法
DOI：
10.18632/oncotarget.2908
复制
发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Qiu L;Li J;Yu S;Wang Q;Li Y;Hu Z;Wu Q;Guo Z;Zhang J
对肿瘤相关碳水化合物抗原（TACAs）的免疫耐受严重限制了大多数TACAs的有效性。为了克服这一问题，我们选择了唾液化的三糖TACA GM3作为靶抗原，并通过代谢生物工程与树突状细胞（DC）疫苗接种相结合，测试了一种新的免疫治疗策略。我们利用n -苯基乙酰- d -甘露糖胺（ManNPhAc）作为生物合成前体，设计癌细胞表达人工结构n -苯基乙酰- d -神经氨酸，以取代天然的n -乙酰- d -神经氨酸。接下来，我们通过用GM3 n -苯乙酰基衍生物脉冲的dc疫苗选择性地靶向生物工程癌细胞。接种装载gm3nphac - klh的dc可产生强大的gm3nphac特异性T细胞依赖性免疫。结果表明，该策略可显著抑制FBL3肿瘤的生长，延长荷瘤小鼠的生存期；B16F10肺转移也可减少。这些发现为克服对TACAs（如GM3）的免疫耐受，开发有效的肿瘤免疫疗法提供了新的策略。
Immune tolerance to tumor-associated carbohydrate antigens (TACAs) has severely restricted the usefulness of most TACAs. To overcome this problem, we selected a sialylated trisaccharide TACA, GM3, as a target antigen, and tested a new immunotherapeutic strategy by combining metabolic bioengineering with dendritic cell (DC) vaccination. We engineered cancer cells to express an artificial structure, N-phenylacetyl-D-neuraminic acid, in place of the natural N-acetyl-D-neuraminic acid of GM3 by using N-phenylacetyl-D-mannosamine (ManNPhAc) as a biosynthetic precursor. Next, we selectively targeted the bioengineered cancer cells by vaccination with DCs pulsed with the GM3 N-phenylacetyl derivative. Vaccination with GM3NPhAc-KLH-loaded DCs elicited robust GM3NPhAc-specific T cell-dependent immunity. The results showed that this strategy could significantly inhibit FBL3 tumor growth and prolong the survival of tumor-bearing mice; B16F10 lung metastases could also be reduced. These findings lay out a new strategy for overcoming immune tolerance to TACAs, such as GM3, for the development of effective tumor immunotherapies.
登录
查看更多内容
影响因子：
--
作者：
Yu S;Wang Q;Zhang J;Wu Q;Guo Z
通讯作者：
Guo Z
影响因子：
11.5
作者：
Krug, LM;Ragupathi, G;Livingston, PO
通讯作者：
Livingston, PO
影响因子：
10.3
作者：
TSUCHIDA, T;SAXTON, RE;IRIE, RF
通讯作者：
IRIE, RF
影响因子：
7.3
作者：
Pan, YB;Chefalo, P;Guo, ZW
通讯作者：
Guo, ZW
影响因子：
4.7
作者：
Wang, Qianli;Ekanayaka, Sandamali Amarasingha;Wu, Jian;Zhang, Junping;Guo, Zhongwu
通讯作者：
Guo, Zhongwu