Peer-Reviewed Publications

All Publications

Cross-Company Evaluation of the Human Lymphocyte Activation Assay

Nonclinical immunotoxicity evaluation is an important component of safety assessment for pharmaceuticals. One in vitro assay that can be applied in a weight of evidence assessment is the human lymphocyte activation (HuLA) assay, an antigen recall assay, similar in many respects to the in vivo T-cell-dependent antibody response (TDAR) in that cooperation of multiple immune cell types are needed to produce responses. This assay uses human cells and is more amenable than the TDAR to compound ranking and mechanistic studies.

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Summary of a Workshop on Preclinical and Translational Safety Assessment of CD3 Bispecifics

Currently, there is a multitude of CD3 bispecifics with different molecular designs and binding properties in preclinical and clinical development for the treatment of liquid or solid tumors. The key safety concerns with CD3 bispecifics are excessive release of cytokines, which may translate to potentially life-threating cytokine release syndrome (CRS), target organ toxicity due to redirection of T-cells to normal tissues expressing the tumor-associated antigen (TAA) (off-tumor/on-target cytotoxicity), and, in some instances, neurotoxicity.

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‘All In’: A Pragmatic Framework for COVID‐19 Testing and Action on a Global Scale

Current demand for SARS‐CoV‐2 testing is straining material resource and labor capacity around the globe. As a result, the public health and clinical community are hindered in their ability to monitor and contain the spread of COVID‐19. Despite broad consensus that more testing is needed, pragmatic guidance towards realizing this objective has been limited. This paper addresses this limitation by proposing a novel and geographically agnostic framework (the 4Ps Framework) to guide multidisciplinary, scalable, resource‐efficient, and achievable efforts towards enhanced testing capacity. The 4Ps (Prioritize, Propagate, Partition, and Provide) are described in terms of specific opportunities to enhance the volume, diversity, characterization, and implementation of SARS‐CoV‐2 testing to benefit public health. Coordinated deployment of the strategic and tactical recommendations described in this framework have the potential to rapidly expand available testing capacity, improve public health decision‐making in response to the COVID‐19 pandemic, and/or to be applied in future emergent disease outbreaks.

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Ontogeny and Cross-Species Comparison of Pathways Involved in Drug Absorption, Distribution, Metabolism, and Excretion in Neonates (Review): Kidney

This review provides insight in cross-species developmental differences of absorption, distribution, metabolism, and excretion properties in the kidney, which should be considered in neonate/juvenile study interpretation, hypotheses generation, and experimental design.

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Cross-Site and Cross-Platform Variability of Automated Patch Clamp Assessments of Drug Effects on Human Cardiac Currents in Recombinant Cells

Automated patch clamp (APC) instruments enable efficient evaluation of electrophysiologic effects of drugs on human cardiac currents in heterologous expression systems. Differences in experimental protocols, instruments, and dissimilar site procedures affect the variability of IC50 values characterizing drug block potency. This impacts the utility of APC platforms for assessing a drug’s cardiac safety margin. We determined variability of APC data from multiple sites that measured blocking potency of 12 blinded drugs (with different levels of proarrhythmic risk) against four human cardiac currents (hERG [IKr], hCav1.2 [L-Type ICa], peak hNav1.5, [Peak INa], late hNav1.5 [Late INa]) with recommended protocols (to minimize variance) using five APC platforms across 17 sites.

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