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Cell Journals Publishes BeyondSpring’s New Data on Mechanism of Plinabulin to Mature Dendritic Cells, Leading to T-Cell Activation
In the Chem article, titled, “Structure, Thermodynamics and Kinetics of Plinabulin Binding to Two Tubulin Isotypes,”1 researchers utilizing x-ray crystallography and thermodynamics calculations demonstrated that Plinabulin as a NCE (new chemical entity) is differentiated from other tubulin-binding agents in both its binding site and the kinetics of the binding. The research also provides evidence that this binding may explain the beneficial efficacy and superior safety profile found with Plinabulin in the clinic, compared to other agents that bind to a nearby colchicine site in tubulin, such as C4AP (combretastatin-A4) or colchicine.
The lead authors of the Chem article include:
In addition to the Chem publication, data on Plinabulin’s ability to positively affect the body’s immune mechanism was published in Cell Reports, titled, “GEF-H1 Signaling upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-tumor Responses.”2 The Cell Reports article demonstrates that Plinabulin destabilizes microtubule and releases immune defense protein GEF-H1, a critical signaling protein for dendritic cell (DC) maturation, antigen cross-presentation and effective priming of CD8 T cells. In the absence of GEF-H1, anti-tumor immunity is hindered. Researchers noted that, in cancer patients, high expression of the GEF-H1 immune gene signature is associated with prolonged survival. Plinabulin is among the most potent tubulin targeted agents for maturing DCs. This highlights Plinabulin’s potential as an ideal partner for combination immuno-oncology approaches seeking to overcome the limitations of checkpoints in treating certain cancers. This finding significantly contributes towards BeyondSpring’s understanding of the durable anti-cancer effects demonstrated to date in nonclinical and clinical testing with Plinabulin.
The lead authors of the Cell Reports article include:
“This journey from the ‘bedside’ back to the ‘benchside’ to uncover Plinabulin's mechanism represents more than five years of international collaborative work with leading institutions. We are grateful to our collaborators and this important recognition by the scientific community that Plinabulin is a first-in-class clinical asset for cancer treatment through an important immune mechanism,” said Dr.
Cautionary Note Regarding Forward-Looking Statements
Source: BeyondSpring, Inc.