Potent Immunotherapeutic Effects of Anti-PD-L1 in an Orthotopic Murine Bladder Tumor Model

Authors

• AJ Vandeveer
• JK Fallon
• KW Hance
• Y Lan
• H Sabzevari
• J Schlom
• JW Greiner

Abstract

In recent years, the emergence in the understanding that inhibitory immune receptors and their ligands play in the ability of tumors to evade an adaptive immune response has been a major advance in clinical immunotherapy. Previous studies illustrated that blocking antibodies for CTLA-4 or PD-1 resulted in clinical responses in many malignancies. PD-L1 has also emerged as a potential target. PD-L1 co-localizes with TILs that express IFNγ. It is hypothesized that PD-L1 induction represents tumor escape from T cell lysis. T cell checkpoint inhibitor efficacy is often increased against tumor types with high mutation rates and a high probability of generating an inherent T cell response. Much of the early attention has focused on Melanoma, NSCLC, and Bladder cancer. Antibodies that block PD-1/PD-L1 interactions have shown efficacy against these cancer types in early-stage clinical trials. In patients diagnosed with Bladder cancer, PD-L1 expression has been reported to correlate with high-grade tumors, a high recurrence rate, and reduced survival rate. The present study was designed to investigate the effects of an anti-PD-L1 antibody in an experimental murine bladder cancer model. Both murine and human (J82, T24, TCCSUP) bladder cancer cell lines express PD-L1 (flow cytometry), and in vitro IFN-γ addition upregulated PD-L1 expression levels on each of those tumor cells. A human IgG1 anti-PD-L1 antibody, Avelumab, was used to study the effects of targeting PD-L1 expression in MB49, murine bladder tumor cells. The model consists of either s.c. tumors or MB49-luc cells instilled intravesically into the bladders of syngeneic mice.

Scientific Focus Area: Immunology

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