IO Summit Europe 2024: Fully Human Conditional Agonist 4-1BB×CD40 Bispecific Antibody Exhibits Potent In Vitro and In Vivo Efficacy
Used in the poster: BsAb Discovery Platform
Summary:
4-1BB and CD40 agonists are promising candidates for cancer immunotherapy but have had limited success due to systemic toxicity risk. We generated a 4-1BB×CD40 bsAb (BCG021) with a more reasonable affinity. BCG021 demonstrated conditional 4-1BB and CD40 agonistic activity and did not show a bell-shaped response as observed for benchmark bsAb. Moreover, BCG021 also exhibited superior in vitro and in vivo efficacy, with ideal physiochemical properties and a better PK profile than the benchmark.
Poster Highlights:
- BCG021 demonstrates conditional 4-1BB and CD40 agonist activity dependent on crosslinking of both targets and without bell-shaped response.
- BCG021 activates immature DCs and stimulates the release of IFN-y from CD4+ T cells cultured with allogeneic DCs.
- BCG021 exhibits potent anti-tumor activity, and significantly improved tumor growth inhibition when combined with anti-PD-1 mAb.
- BCG021 exhibits desirable physicochemical properties, good safety, and an antibody-like PK profile in preclinical mouse models.
