The following article features coverage from the ASCO Gastrointestinal Cancers Symposium 2021 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

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

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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.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO GI 2021 meeting by visiting the conference page.

Reference

  1. Wong DA, Luk MC, Wong TK, Staunton DE, Harlan JM, et al. Efficacy and preclinical safety of ARB202, a potential first-in-class anti-CDH17/CD3 bispecific T-cell engager, for treatment of pancreatic and colorectal cancers. Poster presented at: Gastrointestinal Cancers Symposium; January 15-17, 2021. Abstract 405.
  2. Lum Y-L, Luk JM, Staunton DE, Ng DKP, Fong W-P. Cadherin-17 targeted near-infrared photoimmunotherapy for treatment of gastrointestinal cancer. Mol Pharm. 2020;17(10):3941-3951. doi:10.1021/acs.molpharmaceut.0c00700

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ASCO GI 2021 Gastrointestinal Cancer