Journal
BIOELECTROCHEMISTRY
Volume 140, Issue -, Pages -Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/j.bioelechem.2021.107795
Keywords
Chemokines; CCL5; CCL17; Cytokine expression; Gene electrotransfer; Murine tumors
Funding
- Slovenian Research Agency (ARRS) [J3-8202, P3-0003]
- Republic of Slovenia
- European Regional Development Fund
Ask authors/readers for more resources
The study indicates that gene therapy can alter the distribution of inflammatory cells in the tumor microenvironment and enhance immune system activation. However, further optimization of dosing schedule is needed to achieve better treatment outcomes.
The effectiveness of immunotherapy highly correlates with the degree and the type of infiltrated immune cells in the tumor tissue. Treatments based on modifying the immune cell infiltrate of the tumor microenvironment are thus gaining momentum. Therefore, the aim of our study was to investigate the effects of gene therapy with two proinflammatory chemokines CCL5 and CCL17 on inflammatory cytokine expression profile and immune cell infiltrate in two murine breast tumor models, 4T1 and E0771, and two murine colon tumor models, CT26 and MC38. In vitro, lipofection of plasmid DNA encoding CCL5 or CCL17 resulted in changes in the cytokine expression profile similar to control plasmid DNA, implying that the main driver of these changes was the entry of foreign DNA into the cell's cytosol. In vivo, gene electrotransfer resulted in high expression levels of both Ccl5 and Ccl17 transgenes in the 4T1 and CT26 tumor models. Besides a minor increase in the survival of the treated mice, the therapy also resulted in increased expression of Cxcl9 and Ifnc, potent activators of the immune system, in CT26 tumors. However, this was not recapitulated in changes of TME, implying that a further refinement of the dosing schedule is needed. (C) 2021 The Authors. Published by Elsevier B.V.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available