Abstract LB-219: Derivation of mathematical modeling for the diffusion and penetration of monoclonal antibody delivery into tumor

Abstract

Abstract Background: Commonly malignant solid tumor have an abundant tumor-associated cellular matrix (ECM). Although radioimmunothrepy (RIT) have proven to be effective and precise treatment in cancer, yet RIT has a limited performance in solid tumor, due to highly distributed ECM inside solid tumor tissue. Previously, we designed the combination RIT to enhance the penetration of monoclonal antibody (mAb), where we investigated that, using Relaxin which contain oncolytic adenovirus (OA) as combination therapy decreases tumor associated ECM. In this study, we developed mathematical modeling to explain and describe the diffusion and penetration of mAb inside the tumor with ECM. To obtain the model parameters in our developed mathematical model, we performed related experiments such as immunofluorescence and qRT-PCR. Methods: We developed the reaction-diffusion partial differential equations (PDE) for describing the dependency of cancer cell, ECM density, diffusion and penetration of mAb and ECM modulated therapy that include our experimental data, also to overcome the classical limitation of PDE method. Model included the rapid decrease of ECM by OA, and density dependent diffusion coefficient. Initial condition for solving the PDE was derived using our experimental result. Diffusion coefficient for mAb and OA was modelled for simulating actual behavior of mAb and OA. Various condition of ECM density, and structure were modelled that derives the actual result of distribution of collagen. To confirm the mathematical prediction, we designed in vitro experiment with same condition as used as “in model”. Results: Using our developed model, we successfully described relationship between ECM and mAb transport by OA, and investigated the change of ECM. Diffusion and penetration of mAb and OA were well described from tumor vessel and tumor surface. Regardless of ECM structure, all ECM structure were degraded after spreading of OA. In addition, our model simulation results predicted that mAb uptake dramatically increased in combination approach and was more than mAb alone treatment. Our developed mathematical model predicted the optimal schedule of OA pretreatment and it shows great results more than mAb pretreatment. Pretreatment results with OA shows a great anti-tumor effect more than mAb pretreatment in experimental data. Our model could well predicted and matched the experimental results. Collectively, in our study, we suggested new theoretical mathematical model framework to explain various ECM condition with drug transport Citation Format: Hyeongi Kim, Yangjin Kim, Yong-Jin Lee, Jin-su Kim. Derivation of mathematical modeling for the diffusion and penetration of monoclonal antibody delivery into tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-219.