Publisher: College of Life Sciences and Technology  

Date: November 27, 2024

A research team led by Professor Chen Liang and Associate Researcher Zhou Qian from the Biochemistry Department of the School of Life Sciences and Technology at Jinan University, in collaboration with Professor Ding Ke from the School of Pharmacy, has made a significant contribution to cancer immunotherapy. They published a paper titled, Human/mouse CD137 agonist, JNU-0921, effective shrinkage tumors through enhancing the cytotoxicity of CD8+ T cells in cis and in trans, in the prestigious journal Science Advances (impact factor: 11.7).

 Key Findings

The paper introduces JNU-0921, the first small molecule agonist targeting CD137, a critical receptor involved in T cell activation and immune response. While agonistic antibodies against CD137 have shown promise in shrinking tumors, they have not translated effectively into clinical benefits for cancer patients. This research addresses that gap by detailing the mechanism of JNU-0921 in tumor immunotherapy.

Abstract Highlights:

- JNU-0921 activates both human and mouse CD137 by binding to their extracellular domains, promoting oligomerization and subsequent signaling.

- The compound effectively reduces tumor size in vivo by enhancing the effector and memory functions of cytotoxic CD8+ T cells (CTLs) and reducing T cell exhaustion.

- JNU-0921 shifts helper T cell polarization towards a T helper 1 type, boosting CTL activity, while also diminishing the inhibitory effects of regulatory T cells on CTLs.

 Significance

This research represents a collaborative effort across multiple disciplines within the School of Life Sciences and Technology, overcoming a recognized challenge in the pharmaceutical industry. The elucidation of JNU-0921's mechanism of action and its ability to activate CD137 signaling marks a new era for the development of small molecule agonists, laying a theoretical foundation for future clinical applications.

Corresponding Authors:

- Professor Chen Liang

- Researcher Ding Ke

- Associate Researcher Zhou Qian

Co-First Authors:

- Liu Lu (PhD, postdoctoral student, Jinan University)

- Chen Fenghua (MD, Jinan University)

- Li Shan (PhD, Hangzhou Institute of Medicine, Chinese Academy of Sciences)

- Yang Tong (doctoral student, Jinan University)

For more details, you can access the original paper 

(https://www.science.org/doi/10.1126/sciadv.adp8647).