Antitumor Potential of Extracellular Vesicles Released by Genetically Modified Murine Colon Carcinoma Cells With Overexpression of Interleukin-12 and shRNA for TGF-β1

Frontiers in Immunology
Joanna RossowskaElzbieta Pajtasz-Piasecka

Abstract

Recent developments demonstrate that tumor-derived extracellular vesicles (EVs) could become a highly effective tool for delivery of antitumor factors. The main objective of the study was to determine whether EVs secreted by MC38 colon carcinoma cells genetically engineered for overproduction of interleukin (IL-)12 and/or shRNA targeting TGF-β1 are effectively loaded with these molecules and whether the obtained EVs could be an efficient tool for antitumor therapy. Fractions of EVs released by genetically modified MC38 cells [both modified tumor-derived exosomes (mTEx) and modified microvesicles (mTMv)] and those released by unmodified, wild-type MC38 cells were characterized in terms of loading efficacy, using real-time PCR and ELISA, as well as their antitumor potential. In order to examine the therapeutic potential of mTEx, they were applied in the form of sole treatment as well as in combination with dendritic cell (DC)-based vaccines stimulated with mTMv in the therapy of mice with subcutaneously growing MC38 tumors. The results demonstrated that genetic modification of wild-type MC38 tumor cells is an effective method of loading the molecules of interest into extracellular vesicles secreted by the cells (both TEx and TMv)...Continue Reading

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Citations

Oct 4, 2020·Cancers·Matthen MathewFatemeh Momen-Heravi
Nov 19, 2020·Molecular Oncology·Antonia Schubert, Michael Boutros
Mar 24, 2021·Nature Immunology·Carolyn MararDenis Wirtz

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
genetic modification
PCR
ELISA
flow cytometry
transmission
dynamic
dynamic light scattering
FACS
genetic modifications

Software Mentioned

FACSDiva
FACS Fortessa
NovoExpress
Diva
VectorBuilder

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