A research team led by Professor Yeu Chun Kim and PhD student Seong Dong Jeong from the Department of Chemical and Biomolecular Engineering has yielded a new promising polypeptide that significantly regresses metastasis and induces an antitumor immune response. The research was conducted in collaboration with Professor Chae Ok Yun and Ph.D. student Bo Kyeong Jung from the Department of Bioengineering at Hanyang University. The results were published on February 1 in Advanced Science under the title “Immunogenic Cell Death Inducing Fluorinated Mitochondria-Disrupting Helical Polypeptide Synergizes with PD-L1 Immune Checkpoint Blockade”.  

In the field of cancer immunotherapy, one effective way to treat cancer is utilizing the PD-L1 immune checkpoint blockade to activate the immune response of T cells, a type of white blood cell. This happens through the binding of anti-PD-L1 to PD-L1 to prevent the  stimulation of “programmed death” that deactivates T cells. PD-L1 a.k.a. programmed death-ligand 1 is a transmembrane protein that is found in cancer cells more. However, a critical issue in utilizing this method was that the immune checkpoint blockade fully depended on the presence of T cells to enhance immune response. 

In order to overcome this problem, the research team designed a new polypeptide called “Fluorinated Mitochondria-Disrupting Helical Polypeptide” (MDHPs). As the name suggests, a polypeptide consisting of multiple amino acids is fully saturated with fluorine, forming multiple helical structures. It then puts stress on the endoplasmic reticulum (ER), an organelle in which proteins are folded and secreted, by overloading the ER with the remaining unfolded proteins. This so-called “ER stress” ultimately promotes immunogenic cell death (ICD). ICD includes all types of cell death that elicit an immune response by releasing tumor-associated antigens (TAAs) and danger-associated molecular patterns (DAMPs), substances that send an SOS signal. ICD then activates T cells after a variety of complicated biological processes. Moreover, MDHPs destroy the mitochondrial outer membrane of tumor cells that leads to an increase in reactive oxygen concentration. In other words, they destabilize mitochondria, the powerhouse of the tumor cells, and result in cellular suicide. 

The newly designed polypeptide, used along with PD-L1 immune checkpoint blockade, had a synergic effect of lowering the chance of metastasis to the lungs and increasing the antitumor immune response. Professor Yeu Chun Kim stated, “We look forward to the new various ways to increase the cancer treatment effectiveness through the following development of a new immunogenic cell death.”