Targeting CD47 and Angiogenesis Demonstrates Effective Anti-Tumor Effect in Bladder Cancer

Area of Science:

• Immunology
• Oncology
• Cancer immunotherapy

Background:

• Current bladder cancer immunotherapies have limited response rates, necessitating novel therapeutic targets.
• CD47 is explored as a potential immunotherapy target for bladder cancer due to its role in immune evasion.

Purpose of the Study:

• To evaluate CD47 as a therapeutic target in bladder cancer.
• To investigate the efficacy of combining CD47 blockade with anti-angiogenic therapy.
• To assess a bispecific fusion protein targeting both CD47 and angiogenesis.

Main Methods:

• CD47 protein expression was assessed in 116 bladder cancer tissues using immunohistochemistry (IHC).
• In vitro phagocytosis assays evaluated CD47 blockade effects on macrophage activity.
• In vivo studies utilized the HSPCs-CDX model to test CD47 blockade, anti-angiogenesis, and combination therapies.

Main Results:

• CD47 is highly expressed in bladder cancer and linked to poor prognosis.
• CD47 blockade enhanced macrophage phagocytosis of bladder cancer cells and showed anti-tumor effects (TGI: 33.05%).
• Combination therapy (CD47 blockade + anti-angiogenesis) significantly improved anti-tumor efficacy (TGI: 76.39%), as did a bispecific fusion protein.

Conclusions:

• Targeting CD47 promotes macrophage-mediated anti-tumor immunity in bladder cancer.
• Combined blockade of CD47 and angiogenesis offers a potent immunotherapy strategy for bladder cancer.
• A bispecific fusion protein targeting both pathways demonstrates significant anti-tumor potential.