Anti-4-1BB×CD40 BsAb (BCG021)

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.
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  • Highlights of Anti-4-1BB×CD40 BsAb
  • In Vitro: Conditional 4-1BB and CD40 agonist activity only dependent on crosslinking of both targets
  • In Vivo: BCG021 combination with anti-PD1 significantly improved tumor growth inhibition. Note: BsAb 41BB×CD40 can bind to mouse 4-1BB

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    Highlights of Anti-4-1BB×CD40 BsAb
    • BCG021 demonstrates conditional 4-1BB and CD40 agonist activity only dependent on crosslinking of both targets and without bell-shaped response.
    • BCG021 exhibited potent anti-tumor activity, and significantly improved tumor growth inhibition when combined with Anti-PD1 mAb.
    • BCG021 exhibits desirable physicochemical properties, good safety, and an antibody-like PK profile in preclinical mouse models.
    • Stage: preclinical, CMC to be initiated.
    In Vitro: Conditional 4-1BB and CD40 agonist activity only dependent on crosslinking of both targets

    4-1BB is a costimulatory receptor expressed on activated T cells that enhances their proliferation, survival, and effector functions. It plays a key role in amplifying anti-tumor immune responses, making it a promising target for immunotherapy. However, therapeutic strategies targeting 4-1BB must balance efficacy with potential systemic toxicity.

    In Vivo: BCG021 combination with anti-PD1 significantly improved tumor growth inhibition. Note: BsAb 41BB×CD40 can bind to mouse 4-1BB

    CD40 is a co-stimulatory protein found on antigen-presenting cells such as dendritic cells, B cells, and macrophages. It is crucial for activating the adaptive immune response, including T cell priming and antibody production. Modulating CD40 signaling can boost anti-tumor immunity, but it requires careful control to minimize adverse inflammatory effects.