Nature Immunology is heavy!

On March 26, the internationally renowned journal "Nature Immunology" published an online article "The ubiquitin ligase MDM2 sustains STAT5 stability to control Tcell-mediated antitumor immunity" by Dr.
Shaomeng Wang, co-founder of Yasheng Pharmaceutical and the team of Weiping Zou from the University of Michigan.
This study clarified in detail the new mechanism of MDM2-STAT5 signal axis regulating T cell-mediated tumor immunology.


APG-115 is a new drug under development under Yasheng Pharmaceutical (6855.
HK).
It is an oral bioavailable, highly selective small molecule MDM2-p53 inhibitor with high binding affinity to MDM2 and can be blocked by Interrupting the MDM2-p53 interaction and restoring the tumor suppressor function of p53 plays an important role in tumor development.
However, whether this signaling pathway regulates CD8+T cell-mediated tumor immunity is still unclear.

 In order to further explore the mechanism of the MDM2-p53 signaling pathway in T cells, the researchers constructed a mouse model that specifically knocked out MDM2 and p53 in T cells.

Studies have found that MDM2 regulates the survival and function of CD8+ T cells independent of p53 activity, and MDM2 regulates the stability of STAT5 in CD8+ T cells, which is essential for effective anti-tumor immunity.

 Before the start of this study, it is still unknown whether MDM2-p53 will affect the anti-tumor immune response mediated by CD8+ T cells.
The study found that the E3 ubiquitin ligase MDM2 and p53 interaction pathway is an important T cell immunity.
Therapeutic targets provide new ideas for the future development of cancer immunology.

 Dr.
Yang Dajun, Chairman and Chief Executive Officer of Yasheng Pharmaceutical, said: "This is a truly uncharted territory.

At present, there is an urgent need for targeted drugs that can block the MDM2-p53 interaction and enhance T cell-mediated immunity while eliminating tumor cells.

The publication of this study helps to inspire and help us further accelerate the global development and commercialization of drug candidates.

In view of the series of encouraging safety and efficacy data obtained so far, Asia Pharmaceuticals will speed up the clinical development process and look forward to APG-115 benefiting patients around the world as soon as possible.

"It is reported that Ascent Pharmaceuticals is currently carrying out a phase II clinical trial of APG-115 combined with pembrolizumab to treat patients with tumors who have developed drug resistance or recurrence after PD-1 inhibitor treatment.
The relevant indications include targeting fat Sarcoma, urothelial carcinoma, and malignant peripheral nerve tendon sheath tumor affecting peripheral nerve connective tissue.

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