Catalyst Awardee

Project Description

Senolytic uPAR-CAR-T therapy for osteoarthritis

Chunyi Wen, PhD | The Hong Kong Polytechnic University; Shenzhen University; Li Yu, MD, PhD; Chuan Yu, MS,
Competition Sponsor:
Research Grants Council of the Hong Kong Special Administrative Region, China
Awardee year: 2022


The prerequisite of healthy longevity is the prevention and treatment of age-related diseases. However, pro-inflammatory and fibrosis-inducing tissue microenvironment inevitably leads to tissue damage and chronic disease due to pathologically accumulated senescent cells (SCs) while aging. Fortunately, the urokinase-type plasminogen activator receptor (uPAR) as a promising immune therapy target has recently been identified to eliminate the SCs in mice. But its only been validated in animal models of lung cancer and liver disease. Here, we propose an innovative strategy that uses genetically engineered immune cells, (Chimeric antigen receptor T, CAR-T) to treat osteoarthritis, a common age-related disease, characterized by cartilage degradation, affecting more than 10% of the total population in Hong Kong, and hundreds of millions of people worldwide. We hypothesize that the targeted removal of senescent cells will lead to the significant improvement of osteoarthritis in animal disease models. If successful we will move on to explore the potential of this therapy in many other senescence-associated age-related diseases, including osteoporosis, diabetes, atherosclerosis, COPD, fatty liver diseases, and many more. As a collaborative effort between experts in both age-related diseases and cell therapy, this project could be quickly validated in proof of concept experiments and has the potential to significantly benefit the entire society.

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