Targeting Cadherin-17 (CDH17) and CD3 with a bispecific T-cell engager (BiTE) may be a novel approach for the treatment of pancreatic and colorectal cancers. Promising preclinical study results were presented at the 2021 Gastrointestinal Cancers Symposium.
Aberrant expression of CDH17 is present in 50% to 90% of patients with gastrointestinal cancers. The aim of this study was to develop a BiTE that targets CHD17/CD3 to treat advanced pancreatic and colorectal cancers.1
For the study, the BiTE ARB202 was developed by linking an anti-CDH17 monoclonal antibody to CD3 using a short rigid linker.2 In vitro assays were used to assess preliminary efficacy against normal and cancerous cells. A mouse xenograft model was used to evaluate tumor growth after treatment with ARB202 plus human peripheral blood mononuclear cells (PMBCs) compared with PMBCs alone.1
ARB202 demonstrated cytotoxic effects against CDH17-positive cancer cells but not normal cells or CDH17-negative cancer cells. In a pancreatic xenograft model, tumor growth was inhibited in a dose-dependent manner with ARB202 co-inoculated with human PMBCs. Further, the pharmacokinetic profile of ARB202 was consistent with that of other BiTEs. Toxicity studies found no adverse effects.
Because of these promising findings, “first-in-human studies [are] to be initiated to determine the therapeutic window [for] targeting CDH17 with T-cell engager ARB202,” the study authors concluded.
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