Potential Human Health Hazard of Post-Hurricane Harvey Sediments in Galveston Bay and Houston Ship Channel: A Case Study of Using In Vitro Bioactivity Data to Inform Risk Management Decisions

Natural and anthropogenic disasters may be associated with redistribution of chemical contaminants in the environment; however, current methods for assessing hazards and risks of complex mixtures are not suitable for disaster response. This study investigated the suitability of in vitro toxicity testing methods as a rapid means of identifying areas of potential human health concern. We used sediment samples (n = 46) from Galveston Bay and the Houston Ship Channel (GB/HSC) areas after hurricane Harvey, a disaster event that led to broad redistribution of chemically-contaminated sediments, including deposition of the sediment on shore due to flooding. Samples were extracted with cyclohexane and dimethyl sulfoxide and screened in a compendium of human primary or induced pluripotent stem cell (iPSC)-derived cell lines from different tissues (hepatocytes, neuronal, cardiomyocytes, and endothelial) to test for concentration-dependent effects on various functional and cytotoxicity phenotypes (n = 34). Bioactivity data were used to map areas of potential concern and the results compared to the data on concentrations of polycyclic aromatic hydrocarbons (PAHs) in the same samples. We found that setting remediation goals based on reducing bioactivity is protective of both “known” risks associated with PAHs and “unknown” risks associated with bioactivity, but the converse was not true for remediation based on PAH risks alone. Overall, we found that in vitro bioactivity can be used as a comprehensive indicator of potential hazards and is an example of a new approach method (NAM) to inform risk management decisions on site cleanup.

PD-L1 Inhibitors: Different Classes, Activities, and Mechanisms of Action

Targeting the programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) interaction has become an established strategy for cancer immunotherapy. Although hundreds of small-molecule, peptide, and peptidomimetic inhibitors have been proposed in recent years, only a limited number of drug candidates show good PD-1/PD-L1 blocking activity in cell-based assays. In this article, we compare representative molecules from different classes in terms of their PD-1/PD-L1 dissociation capacity measured by HTRF and in vitro bioactivity determined by the immune checkpoint blockade (ICB) co-culture assay. We point to recent discoveries that underscore important differences in the mechanisms of action of these molecules and also indicate one principal feature that needs to be considered, which is the eventual human PD-L1 specificity.