Research ArticleCancer

Dendritic cell targeting with Fc-enhanced CD40 antibody agonists induces durable antitumor immunity in humanized mouse models of bladder cancer

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Science Translational Medicine  19 May 2021:
Vol. 13, Issue 594, eabd1346
DOI: 10.1126/scitranslmed.abd1346

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Anti-CD40 against bladder cancer

Patients with high-risk non–muscle-invasive bladder cancer can be given intravesical immunotherapy using Bacille Calmette-Guérin (BCG) attenuated bacteria delivered transurethrally, but this treatment is associated with high rates of resistance and recurrence. Garris et al. show that dendritic cells (DCs) in the bladder tumor microenvironment express high levels of CD40 in orthotopic mouse tumor models, consistent with human DCs. Intravesical treatment with an anti-CD40 agonist Ab induces a potent antitumor response in these mouse models that requires conventional DCs and CD8+ T cells. In addition, orthotopic mouse models expressing human CD40 and Fcγ receptors treated with a fully humanized Fc-enhanced anti-CD40 Ab showed potent antitumor responses under naïve and BCG-refractory treatment conditions, suggesting the potential for this treatment to be used clinically.

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