A Systems Pharmacology Model for Drug Delivery to Solid Tumors by Antibody-Drug Conjugates: Implications for Bystander Effects.

ABSTRACT: Antibody-drug conjugates (ADCs) are cancer drugs composed of a humanized antibody linked to a cytotoxic payload, allowing preferential release of payload in cancer cells expressing the antibody-targeted antigen. Here, a systems pharmacology model is used to simulate ADC transport from blood to tumor tissue and ADC uptake by tumor cells. The model includes effects of spatial gradients in drug concentration in a three-dimensional network of tumor blood vessels with realistic geometry and accounts for diffusion of ADC in the tumor extracellular space, binding to antigen, internalization, intracellular processing, and payload efflux from cells. Cells that process an internalized ADC-antigen complex may release payload that can be taken up by other "bystander" cells. Such bystander effects are

SUBMITTER: Burton JK 

PROVIDER: S-EPMC7098807 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature