A Perspective on the Effects of Antigen Shedding on Targeted Delivery of Immunotoxins in Solid Tumors: A Mathematical Model Study

摘要

Most tumor cells express specific antigen molecules, and these antigen molecules are shed from the cell surface. In targeted delivery of anti-cancer agents in tumor tissues, immunotoxins or antibody drug conjugates are designed to kill the target cancer cells. Previously, shed antigens were presumed to be a factor preventing the delivery of immunotoxins to solid tumors, since shed antigens act as a decoy to hinder the effective delivery of toxin molecules in solid tumors. However, a recent mathematical model study showed that antigen shedding could be beneficial for the delivery of immunotoxins. In this work, using this mathematical model, the possible condition in which large antigen shedding positively or negatively affects the efficacy of the delivered immunotoxin was thoroughly investigated in terms of three biological variables: number of surface antigen molecules, endocytosis rate constant, and immunotoxin dose. The present study showed that the positive or negative effect of antigen shedding on the delivery efficiency could be modulated by these three key parameters.