Research Paper Volume 11, Issue 22 pp 10711—10722
p62-DNA-encoding plasmid reverts tumor grade, changes tumor stroma, and enhances anticancer immunity
- 1 Sechenov First Moscow State Medical University, Moscow, Russia
- 2 CureLab Oncology, Inc, Deadham, MA 02026, USA
- 3 Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
- 4 School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy
- 5 Russian Academy of Sciences, Moscow, Russia
- 6 Lomonosov Moscow State University, Moscow, Russia
- 7 Research Center of Family Health and Reproduction Problems, Irkutsk, Russia
- 8 Department of Molecular Biology, Ariel University, Ariel, Israel
- 9 Federal Center of Neurosurgery, Tyumen, Russia
received: September 26, 2019 ; accepted: November 8, 2019 ; published: November 21, 2019 ;https://doi.org/10.18632/aging.102486
How to Cite
Copyright © 2019 Venanzi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Previously, we reported that the administration of a p62/SQSTM1-encoding plasmid demonstrates high safety and signs of clinical benefits for human cancer patients. The treatment also suppressed tumor growth and metastasis in dogs and mouse models. Here we investigated some mechanistic aspects of these effects. In mammary tumors bearing-dogs, i.m. injections of p62 plasmid reduced tumor sizes and their aggressive potential in 5 out of 6 animals, with one carcinoma switching to adenoma. The treatment increased levels of smooth muscle actin in stroma cells and type III collagen in the extracellular matrix, which correlate with a good clinical prognosis. The p62 treatment also increased the abundance of intratumoral T-cells. Because of the role of adaptive immunity cannot be tested in dogs, we compared the protective effects of the p62 plasmid against B16 melanoma in wild type C57BL/6J mice versus their SCID counterpart lacking lymphocytes. The plasmid was only protective in the wild type strain. Also, p62 plasmid amplified the anti-tumor effect of T-cell transfer from tumor-bearing animals to animals challenged with the same tumors. We conclude that the plasmid acts via re-modeling of the tumor microenvironment, making it more favorable for increased anti-cancer immunity. Thus, the p62-encoding plasmid might be a new adjuvant for cancer treatments.