MB5029, αPD-1 x IL-2v Novel Bispecific Fusion Protein
MB5029 is an αPD-1 x non-α and γ attenuated IL-2v bispecific fusion protein designed to selectively target the tumor microenvironment (TME). Attributed to its unique γ attenuated IL-2v and cis-acting mechanism of PD-1, the compound shows strong binding and IL-2 signaling in TME where PD-1 expression is high, while showing weak binding and IL-2 signaling in the peripheral blood, where PD-1 expression is low. MB5029 has demonstrated a dose-dependent anti-tumor efficacy and an excellent safety profile in diverse animal models, setting the compound aside from competitors.
- Biological functions of αPD-1 x non-α IL-2v in PB and TME
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MB5029 potently induces pSTAT5 in activated hPBMC (TME mimicking condition) while showing minimal effect in resting hPBMC (PB mimicking condition). In activated hPBMC, MB5029 exhibits similar levels of T cell activation compared to αPD-1 x non-α IL-2v. However, in resting hPBMC, the degree of T cell activation is markedly reduced, with a 24-fold decrease for αPD-1 x non-α IL-2v and a substantial 2,300-fold decrease for MB5029.
- p-STAT5 of CD8+ T cell in resting & activated hPBMC
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- anti-PD-1 x non-α IL-2
- MB5029
MB5029, potent anti-tumor effect in mouse cancer models
MB5029 exerts potent anti-tumor efficacy in MC38 colon cancer and anti-PD-1 resistant B16F10 melanoma models
- MC38 colon cancer
- B16F10 melanoma
