CMU President Mien-Chie Hung and International Research Team Published Research Findings on the Cancer Research Journal with Their Development of New Target for Immune Checkpoint Therapy
Date：March 30, 2020
A great breakthrough in modern cancer treatment! China Medical University (CMU) President Mien-Chie Hung led an international research team that published their research findings “Targeting Glycosylated PD-1 Induces Potent Anti-tumor Immunity” on the journal Cancer Research. The research finding was published on March 10th, 2020, it was a major breakthrough in cancer treatment and had attracted high attention from the international medical community.
The PD-1 on the surface of immune T cell is an inhibitory receptor. When PD-1 binds with the PD-L1 on the surface of cancer cells and thus ceased the immune T cell’s function in clearing cancer cells, it results in cancer. At present, the anti-PD-1 monoclonal antibody medications can be used to treat various types of cancers but with different responses, and overall the response rate is only around 20%-40%. Two FDA approved anti-PD-1 monoclonal antibody medications- pembrolizumab and nivolumib, did not had expected response in the treatment in many cancer patients although they have both achieved great results in clinical trials. This proves that in clinical use PD-1 still has potential regulatory mechanism that remains unclear.
In this research, the team found out that the PD-1 on immune T cells has been glycosylated in human body, and its state and intensity of glycosylation also vary according to the activation of immune T cells. “Glycosylation modification is an important functional regulatory mechanism after the protein is formed. This induced us to investigate whether the expression pattern of carbohydrates on PD-1 is potentially related to its clinical treatment response.” explain President Hung.
By using the glycoprotein staining and mass spectrometry analysis, the research team proved that PD-1 on immune T cells is highly glycosylated. When glycosylation is removed, it not only reduced the stability of PD-1 but also significantly reduced its binding force with PD-L1. This indicated that the glycosylation of PD-1 plays a crucial role in the interaction with PD-L1, and it may hinder the efficacy of clinical PD-1 antibodies due to complex types of glycosylation, resulting in drug resistance.
“To find a more effective way to block the combination of PD-1 and PD-L1 and to enhance the immunotherapy response to help the patients, we cooperated with STCUBE Inc. and developed a specific monoclonal antibody- STM418. Compared with the current PD-1 antibody medication, STM418 had 3-4 times higher binding affinity to PD-1. STM418 had also achieved good treatment results in animal experiments and had high clinical potentials.” said President Hung.
In summary, this research provided a new insights for the function and significance of PD-1 glycosylation, and provided a theoretical basis for the strategy to develop glycosylated PD-1 as a new target to promote cancer immunotherapy. As for the clinical application, the research team will further explore the therapeutic and diagnostic value of STM418 antibody, and look into the key enzymes that regulate PD-1 glycosylation, in order to find new medication and improve immunotherapy to benefit more cancer patients