Therefore, alternative modelling approaches should be looked for, allowing for more comprehensive analysis with relatively few available experimental data. Rational design of treatment schedules of mAb-based drugs can be accomplished by mechanism-based models. Mathematical models of receptormediated internalization have been developed for peptide ligands and their receptors, and used to analyze targetmediated drug disposition of non mAb-based drugs. So far, mechanism-based models have been successfully developed for unconjugated mAbs, but not for chemotherapy-conjugated mAb-based drugs such as GO. Since conjugated mAb-based drugs are active only upon internalization, the analysis of intracellular drug content dynamics is important for the overall evaluation of drug action. In this work, we present the analysis of a general mechanismbased model for a conjugated mAb-based drug using experimental and clinical data of GO interactions with leukemic XAV939 blasts. The main objectives of the study were, firstly, to evaluate individual parameter values of blast-drug interactions in AML patients and determination of their relative significance for the response to treatment, and, secondly, to propose optimized strategies of GO combined with other cyto-reductive chemotherapeutics for future clinical trials. Three main conclusions can be derived from our analysis. First, pharmacokinetics of targeted drug delivery by GO can be accurately modeled using experimental and clinical data on interactions between GO and AML blast cell. Second, high CD33 antigen production rates and low drug efflux are key factors, determining high intracellular GO exposure. Third, even a modest blast burden reduction may increase intracellular GO exposure and allow the clinical use of a reduced GO dose. Taken together, the presented mechanism-based PK model for GO may be useful in prospectively identifying patients that are most likely to benefit from GO-based therapy, thus improving clinical use of GO. To the best of our knowledge, this is the first research where interaction of a monoclonal antibody-based drug with target cell population was examined in individual patients, assessing PK parameter sensitivity and its significance for individualizing patient treatment schedules. Due to the relatively narrow range of the parameters estimated for different monoclonal antibody-based drugs, our conclusions on the relative importance of certain individually-measurable parameters is probably valid for a wide range of drugs. Therefore, we believe that our approach and our results have a broad pharmacological, pharmaceutical and clinical relevance. We applied a multi-step approach to parameter estimation, which is better suited for systems with parameters of different order of magnitude, as is the case here, than grouping together data taken from experiments of different scales. An AML cell line was employed to measure the previously unreported drugCD33 antigen association and dissociation rates. Since these rates are determined by chemical processes, they are expected to have limited inter-individual variability, similar to that of primary AML cells.