A Quantitative Systems Pharmacology Model Describing the Cellular Kinetic-Pharmacodynamic Relationship for a Live Biotherapeutic Product to Support Microbiome Drug Development.

Live biotherapeutic products (LBPs) are human microbiome therapies showing promise in the clinic for a range of diseases and conditions. Describing the kinetics and behavior of LBPs poses a unique modeling challenge because, unlike traditional therapies, LBPs can expand, contract, and colonize the host digestive tract. Here, we present a novel cellular kinetic-pharmacodynamic quantitative systems pharmacology model of an LBP.

An optimal control approach for enhancing natural killer cells' secretion of cytolytic molecules.

Natural killer (NK) cells are immune effector cells that can detect and lyse cancer cells. However, NK cell exhaustion, a phenotype characterized by reduced secretion of cytolytic models upon serial stimulation, limits the NK cell's ability to lyse cells. In this work, we investigated strategies that counteract the NK cell's reduced secretion of cytolytic molecules.

Enhancing network activation in natural killer cells: predictions from in silico modeling.

Natural killer (NK) cells are part of the innate immune system and are capable of killing diseased cells. As a result, NK cells are being used for adoptive cell therapies for cancer patients. The activation of NK cell stimulatory receptors leads to a cascade of intracellular phosphorylation reactions, which activates key signaling species that facilitate the secretion of cytolytic molecules required for cell killing.

Modeling immune cell behavior across scales in cancer.

Detailed, mechanistic models of immune cell behavior across multiple scales in the context of cancer provide clinically relevant insights needed to understand existing immunotherapies and develop more optimal treatment strategies. We highlight mechanistic models of immune cells and their ability to become activated and promote tumor cell killing. These models capture various aspects of immune cells: (a) single-cell behavior by predicting the dynamics of intracellular signaling networks in individual immune cells, (b) multicellular interactions between tumor and immune cells, and (c) multiscale dynamics across space and different levels of biological organization.