Research Projects

Cancer immunotherapy is one of the emerging approaches to combat different types of cancers. In comparison with conventional cancer treatment modalities, immunotherapy activates the host immune system to fight against pathogens such as cancer. The activation of immune system stimulates innate/adaptive immune response with durable immunological memory effect. It was also known that many different cancer treatment modes such as chemotherapy, radiotherapy and photodynamic therapy can in fact induce immune response to certain extent and elicit immunogenic cell death (ICD). ICD is a distinct way of inducing cancer cell death that was regulated by active immune response. In general, cancer cells evade immune response by engaging in crosstalk with immune cells. Therefore, it is important to identify such crosstalk and inhibit them is essential for the immune system to identify the pathogens. Immune check point inhibitors (ICIs) block the survival communication between cancer cells and immune cells by targeting immune check point proteins. Programmed cell death-1 (PD-1) and programmed cell death-ligand1 (PD-L1) proteins are the well-studied checkpoint proteins inhibit T cell activation and promote immune evasion. Moreover, the overexpression of PD-L1 protein was reported in several solid tumors, making it a potential target for inducing immune response. Currently, three PD-L1 antibodies (atezolizumab, durvalumab and avelumab) are approved by the U.S. Food and Drug Administration (FDA) for clinical use. Monoclonal antibodies-based immunotherapy has significantly improved the survival rate of cancer patients suffering from different types of tumors. But only a small subset of cancer patients responded well to immunotherapy treatment, whereas most of the patients’ response rate was poor. It was noted that the tumor associated antigens (TAAs) present on tumor cells surface is important to elicit immune response. Therefore, only patients who express TAAs will respond to immunotherapy further limits its potential. In addition to this, monoclonal antibodies also suffer several shortcomings such as poor pharmacokinetics, less permeable, lack of oral bioavailability, tedious production process, special storage conditions and high cost. To address these issues, I propose to design photoactive Ir(III)/ Pt(IV) prodrugs containing PD-L1 inhibitor to induce photocytotoxicity, immunogenic cell death (ICD) and Immune check point inhibition (ICI) to harness the potential to develop a combinational photoimmunotherapeutic approach to combat against superficial cancers with spatio-temporal precision.