2020 Grantee: Xiaoyang Qi, PhD
University of Cincinnati
Research Project: Immunotherapy for Pancreatic Cancer by Saposin C-based Nanovesicles
Award: 2020 Pancreatic Cancer Action Network Translational Research Grant
Award Period: Sept. 1, 2020 – Aug. 31, 2022
Dr. Xiaoyang Qi received his PhD from Oklahoma State University in 1992. Dr. Qi is presently working as a professor in the division of hematology-oncology in the department of internal medicine and the division of human genetics in the department of pediatrics at University of Cincinnati College of Medicine. Dr. Qi is also director of the Brain Tumor Modeling Program, the Brain Tumor Center, Gardner Neuroscience Institute, and a professor in the biomedical engineering program in the College of Engineering, University of Cincinnati.
Dr. Qi’s research is focused on developing a novel SapC-DOPS nanovesicle (small sac to deliver drugs), which has the potential to offer a targeted, potent, broad and safe therapeutic agent for cancer patients. In preclinical studies, these stable nanovesicles have shown tumor-specific targeting activity and cancer-selective killing efficacy in various animal tumor models.
He has published more than 150 publications in peer-review journals and scientific abstracts. He is a senior member of National Academy of Inventors. A total of 18 patents have been issued, and more than 25 patents were filed in his name. The translational research in Dr. Qi’s laboratory has led to the development of BXQ-350 (SapC-DOPS) for the first-in-human clinical trials by Bexion Pharmaceuticals in the U.S.
An exciting area of research that has great potential for improving outcomes for pancreatic cancer patients is understanding the role of the immune system in fighting the disease. In normal circumstances, the immune system plays a key role in preventing the formation and growth of tumors. It is now well established that many cancers, including pancreatic cancer, generate a localized tumor microenvironment (TME) that allows the cancer to escape the normal immune surveillance system.
The overall objective of Dr. Qi’s proposal is to evaluate a new preclinical treatment for pancreatic cancer that directly reverses the TME immune suppression. The team’s studies show that pancreatic tumors secrete Heat Shock Protein 70 (sHsp70), which markedly stimulates the conversion of immune cells called macrophages to a polarized form that are immunosuppressive (block an immune response to the cancer cells).
Dr. Qi and colleagues have preliminary data that blocking sHsp70 with either neutralizing antibodies or with nanoparticles containing an agent, SapC-DOPG, completely reverses the immune suppression. In Aim 1 of this proposal, they will confirm that SapC-DOPG nanovesicles are specific to the cancer cells and cause minimal toxicity (side effects). In Aim 2, they will use pancreatic cancer mouse models to assess how SapC-DOPG nanovesicles affect sHsp70, macrophage polarization and tumor growth.
Importantly, as a variant of SapC-DOPG has already successfully completed a phase 1 trial in brain tumor patients, the results from this preclinical study in mice could be rapidly applied to humans.