Shanghai and Hong Kong – September 16, 2026 -- Antengene Corporation Limited (SEHK: 6996.HK) has published preclinical data showing that combining its CD73 inhibitor ATG-037 with selinexor suppressed tumor growth by 62% in a multiple myeloma mouse model, versus 31% for ATG-037 alone and 43% for selinexor alone. The peer-reviewed paper, developed with the Department of Hematology at Peking University Third Hospital, appears in Cancer Gene Therapy, an SCI journal under Springer Nature (DOI: 10.1038/s41417-026-01078-9).
Selinexor treatment upregulates CD73, creating a resistance pathway the combination targets
Researchers found that selinexor treatment raised CD73 expression across most tested tumors, a mechanism linked to adenosine accumulation and an immunosuppressive tumor microenvironment. The study used a J558-inoculated BALB/c mouse model with four treatment arms—vehicle, ATG-037 monotherapy, selinexor monotherapy, and combination therapy—to test whether blocking CD73 could counter this resistance mechanism.
Single-cell sequencing links combination therapy to CD8+ T cell activation via CD80–CD28 signaling
Single-cell RNA sequencing showed the combination synergistically potentiated CD8+ T cell activation by strengthening interactions between CD8+ T cells and Enpp1+ cells through the CD80–CD28 signaling pathway. Immunofluorescence staining confirmed increased CD8+ T cell infiltration into tumor tissue under combination treatment.
Co-culture experiments show elevated Granzyme B and IFN-γ levels in combination-treated cells
In co-culture models pairing CD8+ T cells with multiple myeloma cell lines, CD73 inhibition strengthened selinexor-mediated tumor cell killing by activating CD8+ T cells. The combination group showed significantly elevated Granzyme B (P=0.0252) and IFN-γ (P=0.0067) compared with other treatment arms.
The study's authors conclude that combining selinexor with a CD73 inhibitor blocks an immunosuppressive feedback loop driven by CD73-dependent adenosine synthesis, restoring CD8+ T cell activation and proliferation. Antengene positions the approach as a therapeutic paradigm for addressing drug resistance and refractory multiple myeloma cases.