A Computer-Based Method to Rapidly Analyze Tumor Cell Lysis In. Vivo

Abstract

A discrete-event, compartmentalized, stochastic, computer-based simulation technique using GPSS-H was developed that made it possible to quantify key parameters of tumor cell lysis in vivo. Tests are complete within 24 hr and use relatively small numbers of mice. For the key tissue compartments (whole body, lungs, blood, spleen, liver, bone marrow and lymph nodes) the main tumor cell parameters were: residence times; probability of lysis; accumulative lysis; and rate constants for lysis. The modeling approach also included the capability to quantify T cell, NK cell, and macrophage-mediated tumor cell lysis, and how drugs affected these lytic processes. The evidence presented indicates that the approach appears to provide a rapid and effective means to screen drugs for their effectiveness in vivo, to quantify how drugs affect immune-mediated tumor cell lysis, and a means to quantify how cancer treatment modalities affect these parameters. The approach also appears to be generally applicable to pharmacokinetic and pharmacodynamic studies in vivo.