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Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas

Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Department of Oncology, University of Torino, 10043 Orbassano, Italy
Institute of Biostructures and Bioimaging (IBB), Italian National Research Council (CNR), 10126 Torino, Italy
Authors to whom correspondence should be addressed.
Vaccines 2020, 8(2), 166;
Received: 31 January 2020 / Revised: 31 March 2020 / Accepted: 1 April 2020 / Published: 6 April 2020
(This article belongs to the Special Issue Immunization by Electroporation)
Non-small cell lung cancer (NSCLC) is still the leading cause of cancer death worldwide. Despite the introduction of tyrosine kinase inhibitors and immunotherapeutic approaches, there is still an urgent need for novel strategies to improve patient survival. ROS1, a tyrosine kinase receptor endowed with oncoantigen features, is activated by chromosomal rearrangement or overexpression in NSCLC and in several tumor histotypes. In this work, we have exploited transgenic mice harboring the activated K-Ras oncogene (K-RasG12D) that spontaneously develop metastatic NSCLC as a preclinical model to test the efficacy of ROS1 immune targeting. Indeed, qPCR and immunohistochemical analyses revealed ROS1 overexpression in the autochthonous primary tumors and extrathoracic metastases developed by K-RasG12D mice and in a derived transplantable cell line. As proof of concept, we have evaluated the effects of the intramuscular electroporation (electrovaccination) of plasmids coding for mouse- and human-ROS1 on the progression of these NSCLC models. A significant increase in survival was observed in ROS1-electrovaccinated mice challenged with the transplantable cell line. It is worth noting that tumors were completely rejected, and immune memory was achieved, albeit only in a few mice. Most importantly, ROS1 electrovaccination was also found to be effective in slowing the development of autochthonous NSCLC in K-RasG12D mice. View Full-Text
Keywords: DNA plasmid electroporation; ROS1; NSCLC DNA plasmid electroporation; ROS1; NSCLC
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MDPI and ACS Style

Riccardo, F.; Barutello, G.; Petito, A.; Tarone, L.; Conti, L.; Arigoni, M.; Musiu, C.; Izzo, S.; Volante, M.; Longo, D.L.; Merighi, I.F.; Papotti, M.; Cavallo, F.; Quaglino, E. Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas. Vaccines 2020, 8, 166.

AMA Style

Riccardo F, Barutello G, Petito A, Tarone L, Conti L, Arigoni M, Musiu C, Izzo S, Volante M, Longo DL, Merighi IF, Papotti M, Cavallo F, Quaglino E. Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas. Vaccines. 2020; 8(2):166.

Chicago/Turabian Style

Riccardo, Federica, Giuseppina Barutello, Angela Petito, Lidia Tarone, Laura Conti, Maddalena Arigoni, Chiara Musiu, Stefania Izzo, Marco Volante, Dario L. Longo, Irene F. Merighi, Mauro Papotti, Federica Cavallo, and Elena Quaglino. 2020. "Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas" Vaccines 8, no. 2: 166.

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