Combining 4-1BB agonism with S100A9 inhibition improves T cell activation and tumor control in multiple myeloma models, indicating new immunotherapy potential.
Key Points
To assess the therapeutic effects of IgG2a-formatted 4-1BB agonism with S100A9 inhibition on T cell activation and tumor control in multiple myeloma.
Investigated 4-1BB expression using single-cell RNA sequencing in 5T33MM mice.
Evaluated therapeutic effects of 4-1BB agonists LOB12.3 and 3H3 in 5TGM1 mice.
Administered Tasquinimod alongside the lead 4-1BB agonist to assess combined effects on tumor microenvironment.
Monitored tumor burden via plasmacytosis measurement and serum electrophoresis.
4-1BB agonists significantly increased CD4+ and CD8+ T cells in the bone marrow and spleen.
Clone 3H3 decreased M-protein levels and BM plasmacytosis significantly (p<0.01).
Combination of IgG2a-formatted 4-1BB agonist and TasQ reduced M-protein levels by a significant margin (p<0.0001).
Treatment enhanced T and NK cell activation, indicated by increased granzyme B and effector T cell differentiation.