Synthesis And Immunological Evaluation Of Anti-Cancer Carbohydrate Vaccine Covalently Conjugating With Agonist Of Natural Killer T Cell (KRN7000)

Tumor associated carbohydrate antigens(TACAs)are considered as a valuable target of anti-cancer vaccine,attracting the attention of the community of anti-cancer immunotherapy.How to trick the immune system to break tolerance and induce a response to tumor-associated carbohydrate antigens(TACAs),especially to elicit high titers of high-affinity IgG antibodies is a key problem remained to be solved in the field of TACA-based anti-cancer vaccine.The strategy of adjuvant is one of the keys to solve this problem,a-galactosylceramide(lKRN7000)and its glycolipid analogs are the agonists of NKT cells,which were usually employed as adju'vants in the development of vaccines,but were seldom used as build-in adjuvants(adjuvant covalently links with antigen moiety).Based on the immune-modulating effect of KRN7000 and in-depth study of NKT cells,NKT cells are able to help B cell response in a similar mechanism to T helper cells,stimulating TACA-specific B cells to switch to IgG production.Our central hypothesis is that without incorporating the T cell epitope(usually peptide),using KRN7000 as build-in adjuvant,which covalently linked with TACAs,will enhance the immunological response to TACAs.The purpose of my research in this dissertation is to study whether covalent incorporation of KRN7000 to TACAs will have a positive effect on class switch of antibody from IgG.My research in this dissertation included:(1)Two fully synthetic anti-cancer vaccine were designed and synthesized,in which STn,Tn are covalently linked to KRN7000 respectively;(2)One vaccine(STn-KRN7000)was evaluated for the immunological activity via ELISA.The preliminary results show that STn-KRN7000 can effectively achieve high IgM to IgG antibody class switch.These results pave the road for the NKT cell related vaccine development in the future.