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ADCs White Paper-1

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Assay Platforms to Assess Off-Target Toxicity or Linker Stability Caused by Antibody Drug Conjugates (ADCs)

E. Clarke, ReachBio, Seattle, WA, USA

ADCs combine the benefits of both therapeutic antibodies and potent small molecule cytotoxic drugs. These moieties are connected through linkers that should be stable within systemic circulation but which cleave within the antibody-targeted cells, to release highly specific drugs. With more complex structures come more biological challenges. We have assays to test for:
Off-target toxicity to progenitor cells using the colony forming cell (CFC) assay
Linker stability using a neutrophil differentiation assay (Zhao et al, 2017)

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A Platform for Screening Drugs  to Treat Sickle Cell Disease and Other Hemoglobinopathies

S. Haugabook, NCATS, Bethesda, MD, USA,

E. Clarke + G. dos Santos, ReachBio, Seattle, WA, USA

This serum-free assay platform offers a direct measurement of the HbF protein, using two methods in response to treatment with HU as shown, and additionally with other HbF inducers. This differs from other approaches looking atincreases in transcript numbers or other indirect measurements. This in vitro assay will facilitate the ability to examine new potential drug therapies, both alone and in combination with HU, on HbF induction. This assay may be used to assess HU responsiveness in some SCD patients and to identify other patient-specific drug options.

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PBMC Tips and Tricks

E. Clarke + G. dos Santos, ReachBio, Seattle, WA, USA

To summarize, PBMCs are readily available and provide a relevant cell population for addressing many biological queries. With a little additional attention to detail in cell preparation and cell storage, the data generated from viable PBMCs may provide a wealth of information about normal versus diseased and treated versus untreated patients, and information regarding potential drug candidates with an increased understanding of underlying mechanisms.