Synthesis of DNP-modified GM3-based anticancer vaccine and evaluation of its immunological activities for cancer immunotherapy  

作　　者：Han Lin Haofei Hong Lipeng Feng Jie Shi Zhifang Zhou Zhimeng Wu 

机构地区：[1]Key Laboratory of Carbohydrate Chemistry&Biotechnology,Ministry of Education,School of Biotechnology,Jiangnan University,Wuxi 214122,China

出　　处：《Chinese Chemical Letters》2021年第12期4041-4044,共4页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China (Nos. 21907038, 32000904);the Natural Science Foundation of Jiangsu Province (No. BK20200601, China);the National Postdoctoral Program for Innovative Talents of China (No. BX20200153);the Health and Family Planning Commission of Wuxi, China (No. Z202005);the Social Development Key Project of Jiangsu Province (No. BE2019632, China);partly supported by the 111 Project (No. 111-2-06, China);the National First-class Discipline Program of Food Science and Technology (No. JUFSTR20180101, China)。

摘　　要：Tumor-associated carbohydrate antigens(TACAs) are attractive targets for vaccine development. In this context, we described a strategy combining artificial TACA and glycoengineering for cancer vaccine development. A 2,4-ditrophenyl(DNP)-modified GM3 intermediate was synthesized chemoenzymatically and conjugated to keyhole limpet hemocyanin(KLH), and the resulting bioconjugate was tested for its potential as a vaccine candidate. Mice immunological studies revealed that the DNP-modified GM3(GM3-NHDNP) analog elicited strong and rapid immune responses by recruiting anti-DNP antibodies to facilitate the targeted delivery of the vaccine construct to antigen processing cells(APCs). Moreover, the endogenously produced anti-DNP antibodies, together with the elicited antibodies against GM3-NHDNP, may synergistically promote tumor binding and cancer cell death when the cancer cell surfaces are glycoengineered to express the GM3-NHDNP antigen.

关 键 词：GM3 Cancer vaccine Anti-DNP antibodies GLYCOENGINEERING Tumor-associated carbohydrate antigen 

分 类 号：TQ464[化学工程—制药化工]