MECHANICAL HETEROGENIZATION OF LEWIS LUNG CARCINOMA CELLS CAN IMPROVE ANTIMETASTATIC EFFECT OF DENDRITIC CELLS

Abstract

The effect of mechanically heterogenized (MCH) microparticles of tumor cells (TCs) on antimetastatic action of dendritic cells (DCs) is studied in C57BL/6 mice with Lewis' carcinoma. DCs isolated from mice spleens and loaded with MCH-TCs are analyzed with flow cytometry methods. MCH-TCs are analyzed with optical and/or electron microscopy. The paper describes an original high-precision medical microvibromill with high-acceleration linear induction motor that generates magnetic levitation to produce mechanical heterogenization of TCs. MCH-TCs have a more asymmetric morphology, larger surface and higher internal structure heterogeneity, and higher concentration of free radicals with respect to conventionally treated TCs. The rate of DCs maturity, being affected by pre-incubation with MCH-TCs is found to be higher than its counterpart treated with conventional TCs. DCs loaded with MCH-TCs show a significantly higher ability to induce proliferation of allogeneic lymphocytes in mixed leukocyte reaction. The inhibition index of metastases formation increases from 42% (conventional TCs) to 66% when DCs are treated with MCH-TCs. The present results demonstrate the feasibility of increasing antimetastatic activity of DCs-based vaccines when MCH-TCs is used for their loading. Mathematical model is developed in order to simulate the processes of capture, processing and presentation of tumor antigens by DCs when using conventional TCs or MCH-TCs.