Glycoengineering Antibody and Antibody-dependent Cell-mediated Cytotoxicity (ADCC) Enhancement and Antibody-mediated Vaccinal Effect. In our previous study, Antibody has homologous glycosylation that can increase the affinity to the Fc receptor to enhance ADCC functions in NK cells. This finding is good for improving the antibody-drug design and efficiency. In addition, we found that the antibody treatment with tumors or influenza will generate a memory immune response to protect the host against recurrence and infection. However, the mechanism is not clear so far. Therefore, we are going to establish the animal model to study this antibody-mediated vaccinal effect and to figure out the regulatory mechanism. Desialylation and Immune Checkpoint Therapy Design. Dr. Carolyn Bertozzi was awarded the 2022 Nobel Prize in Chemistry. In her recent studies, she found that the sialo-glycans will inhibit the NK cell functions by negative regulatory signaling on the NK cell surface to suppress the ADCC functional activity or other positive regulatory immune attacks. However, there are no defined glycans and receptors involved in these inhibitory reactions. According to this hypothesis, our research group found that Siglec 9 plays an important receptor in interacting with sialo-glycans to suppress NK cell functions. The effect of this interaction is similar to PD1-PDL1 immune suppression. Thus, In this study, we are going to examine several approaches to block immunosuppression, such as antibody development, inhibitor, and desialylation therapy to select the best way for immune therapy. Anti-SSEA3 Humanized Antibody Development and Antibody-dependent Cellular Phagocytosis (ADCP). In our current study, we found that the glycoengineering antibody is able to promote the ability of M1 macrophages for phagocytosis. M1 macrophage expressed Fc gamma RI receptor and Fc gamma RIIIA receptor, However Fc gamma RI receptor have obviously stronger binding with antibody than Fc gamma RIIIA receptor. Therefore, We are going to investigate and develop the Fc domain and optimal glycans that specifically bind to the Fc gamma RI receptor to destroy the tumor mass or tumor stem cells and increase the antibody-mediated vaccinal effect. I would like to bring the novel knowledge of glycobiology, oncology, and immune therapy back to Taiwan, especially the correlation between cellular biochemistry and glycoscience. In my current research, we found that the tumor cells not only need highly glycosyl metabolism pathways for survival but also express specific glycans for promoting cancer survival signals and escaping immune cell attacks (known as immunosuppression).  On the other hand, we are making an effort to enhance antibodies' effectiveness and antibody-vaccinal effects by glycosyl-engineering on the Fc domain in the animal study. This modification made human immune cells quickly recognize antibodies and increased binding affinity for ADCC(Antibody-dependent cellular cytotoxicity) or ADCP(Antibody-dependent cellular phagocytosis).