Modeling to capture bystander-killing effect by released payload in target positive tumor cells.

ABSTRACT:

Background

Antibody-drug conjugates (ADCs) are intended to bind to specific positive target antigens and eradicate only tumor cells from an intracellular released payload through the lysosomal protease. Payloads, such as MMAE, have the capacity to kill adjacent antigen-negative (Ag-) tumor cells, which is called the bystander-killing effect, as well as directly kill antigen-positive (Ag+) tumor cells. We propose that a dose-response curve should be independently considered to account for target antigen-positive/negative tumor cells.

Methods

A model was developed to account for the payload in Ag+/Ag- cells and the associated parameters were applied. A tumor growth inhibition (TGI) effect was explored based on an ordinary differential equation (ODE) after substituting the payl

SUBMITTER: Byun JH 

PROVIDER: S-EPMC6399851 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature