#China #Shanghai #Antengene #Selinexor #ATG-037

Antengene's Groundbreaking Research on Cancer Treatment

Antengene Corporation Limited, a prominent biotech firm listed on the Hong Kong Stock Exchange, has made significant strides in cancer research following the publication of its preclinical study in the esteemed journal, Cancer Gene Therapy. This research explored the impact of their CD73 small molecule inhibitor, ATG-037, when combined with selinexor for the treatment of multiple myeloma (MM).

Background of the Study

The study was conducted in association with the Department of Hematology at Peking University Third Hospital. The focus was to evaluate how ATG-037 could boost the anticancer effects of selinexor, particularly against MM, a type of blood cancer.

In a detailed examination, the researchers first assessed the expression of CD73 across various tumor cell lines after treatment with selinexor. They then tested the combined approach in live animal models, specifically using a J558-inoculated BALB/c mouse model. The mice were divided into several groups: a vehicle control, a group receiving ATG-037 alone, one for selinexor alone, and a combination therapy group.

Key Findings

One of the striking findings of the study was that selinexor tends to increase the levels of CD73 in tumors, which is part of a mechanism that can lead to resistance against treatment. The mice treated with the combination of ATG-037 and selinexor demonstrated a tumor growth inhibition rate of 62%. In comparison, the inhibition rates for the ATG-037 and selinexor monotherapy were just 31% and 43%, respectively.

Single-cell RNA sequencing played a pivotal role in analyzing the immune cell subtypes and understanding the dynamics of tumor-immune interaction. Interestingly, the combination therapy was found to enhance the activation of CD8+ T cells. This was attributed to improved interactions between CD8+ T cells and Enpp1+ cells via the CD80-CD28 signaling pathway. The immunofluorescence staining of tumor tissues further confirmed a notable increase in CD8+ T cell infiltration following combination treatment.

Moreover, in co-culture experiments simulating the tumor environment, the inhibition of CD73 significantly enhanced the effectiveness of selinexor by fortifying CD8+ T cell-mediated tumor cell lysis. Noteworthy increases in Granzyme B and IFN-γ levels in the combination group highlighted the enhanced antitumor activity.

Conclusion

The implications of this research are profound, indicating that the combination of selinexor with a CD73 inhibitor like ATG-037 could serve as a promising novel therapeutic strategy against drug resistance in multiple myeloma. By disrupting the immunosuppressive landscape fostered by CD73, the combination approach reinvigorates CD8+ T cell activation and thereby augments their tumoricidal capabilities.

This groundbreaking work establishes a fresh clinical pathway, potentially benefiting patients grappling with refractory MM and contributing to the ongoing evolution of cancer therapies.

About Antengene

Antengene is on the frontier of biotech innovation, concentrating on the development of first-in-class and best-in-class therapeutics for various diseases, including oncology and autoimmune disorders. Their research pipeline is extensive, containing investigational compounds ranging from preclinical to commercial stages. Some notable candidates include ATG-022, ATG-101, and of course, ATG-037. As part of their mission, Antengene seeks to satisfy unmet medical needs globally while maintaining a commitment to rigorous research and development protocols.

With 34 investigational new drug approvals already secured in the U.S. and Asia, along with various new drug applications across multiple markets, Antengene's trajectory suggests a robust presence in the landscape of modern medicine. Their flagship product, selinexor, is already approved in numerous Asia Pacific markets and reflects their dedication to enhancing patient care and treatment outcomes in oncology.