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Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding vector
Autophagy plays an important role in neoplastic transformation of cells and in resistance of cancer cells to radio- and chemotherapy. p62 (SQSTM1) is a key component of autophagic machinery which is also involved in signal transduction. Although recent empirical observations demonstrated that p62 is...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858567/ https://www.ncbi.nlm.nih.gov/pubmed/24121124 |
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author | Venanzi, Franco Shifrin, Victor Sherman, Michael Y. Gabai, Vladimir Kiselev, Oleg Komissarov, Andrey Grudinin, Mikhail Shartukova, Maria Romanovskaya-Romanko, Ekaterina A. Kudryavets, Yuri Bezdenezhnykh, Natalya Lykhova, Oleksandra Semesyuk, Nadiia Concetti, Antonio Tsyb, Anatoly Filimonova, Marina Makarchuk, Victoria Yakubovsky, Raisa Chursov, Andrey Shcherbinina, Vita Shneider, Alexander |
author_facet | Venanzi, Franco Shifrin, Victor Sherman, Michael Y. Gabai, Vladimir Kiselev, Oleg Komissarov, Andrey Grudinin, Mikhail Shartukova, Maria Romanovskaya-Romanko, Ekaterina A. Kudryavets, Yuri Bezdenezhnykh, Natalya Lykhova, Oleksandra Semesyuk, Nadiia Concetti, Antonio Tsyb, Anatoly Filimonova, Marina Makarchuk, Victoria Yakubovsky, Raisa Chursov, Andrey Shcherbinina, Vita Shneider, Alexander |
author_sort | Venanzi, Franco |
collection | PubMed |
description | Autophagy plays an important role in neoplastic transformation of cells and in resistance of cancer cells to radio- and chemotherapy. p62 (SQSTM1) is a key component of autophagic machinery which is also involved in signal transduction. Although recent empirical observations demonstrated that p62 is overexpressed in variety of human tumors, a mechanism of p62 overexpression is not known. Here we report that the transformation of normal human mammary epithelial cells with diverse oncogenes (RAS, PIK3CA and Her2) causes marked accumulation of p62. Based on this result, we hypothesized that p62 may be a feasible candidate to be an anti-cancer DNA vaccine. Here we performed a preclinical study of a novel DNA vaccine encoding p62. Intramuscularly administered p62-encoding plasmid induced anti-p62 antibodies and exhibited strong antitumor activity in four models of allogeneic mouse tumors – B16 melanoma, Lewis lung carcinoma (LLC), S37 sarcoma, and Ca755 breast carcinoma. In mice challenged with Ca755 cells, p62 treatment had dual effect: inhibited tumor growth in some mice and prolonged life in those mice which developed tumor size similar to control. P62-encoding plasmid has demonstrated its potency both as a preventive and therapeutic vaccine. Importantly, p62 vaccination drastically suppressed metastasis formation: in B16 melanoma where tumor cells where injected intravenously, and in LLC and S37 sarcoma with spontaneous metastasis. Overall, we conclude that a p62-encoding vector(s) constitute(s) a novel, effective broad-spectrum antitumor and anti-metastatic vaccine feasible for further development and clinical trials. |
format | Online Article Text |
id | pubmed-3858567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-38585672013-12-11 Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding vector Venanzi, Franco Shifrin, Victor Sherman, Michael Y. Gabai, Vladimir Kiselev, Oleg Komissarov, Andrey Grudinin, Mikhail Shartukova, Maria Romanovskaya-Romanko, Ekaterina A. Kudryavets, Yuri Bezdenezhnykh, Natalya Lykhova, Oleksandra Semesyuk, Nadiia Concetti, Antonio Tsyb, Anatoly Filimonova, Marina Makarchuk, Victoria Yakubovsky, Raisa Chursov, Andrey Shcherbinina, Vita Shneider, Alexander Oncotarget Research Paper Autophagy plays an important role in neoplastic transformation of cells and in resistance of cancer cells to radio- and chemotherapy. p62 (SQSTM1) is a key component of autophagic machinery which is also involved in signal transduction. Although recent empirical observations demonstrated that p62 is overexpressed in variety of human tumors, a mechanism of p62 overexpression is not known. Here we report that the transformation of normal human mammary epithelial cells with diverse oncogenes (RAS, PIK3CA and Her2) causes marked accumulation of p62. Based on this result, we hypothesized that p62 may be a feasible candidate to be an anti-cancer DNA vaccine. Here we performed a preclinical study of a novel DNA vaccine encoding p62. Intramuscularly administered p62-encoding plasmid induced anti-p62 antibodies and exhibited strong antitumor activity in four models of allogeneic mouse tumors – B16 melanoma, Lewis lung carcinoma (LLC), S37 sarcoma, and Ca755 breast carcinoma. In mice challenged with Ca755 cells, p62 treatment had dual effect: inhibited tumor growth in some mice and prolonged life in those mice which developed tumor size similar to control. P62-encoding plasmid has demonstrated its potency both as a preventive and therapeutic vaccine. Importantly, p62 vaccination drastically suppressed metastasis formation: in B16 melanoma where tumor cells where injected intravenously, and in LLC and S37 sarcoma with spontaneous metastasis. Overall, we conclude that a p62-encoding vector(s) constitute(s) a novel, effective broad-spectrum antitumor and anti-metastatic vaccine feasible for further development and clinical trials. Impact Journals LLC 2013-10-02 /pmc/articles/PMC3858567/ /pubmed/24121124 Text en Copyright: © 2013 Venanzi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Paper Venanzi, Franco Shifrin, Victor Sherman, Michael Y. Gabai, Vladimir Kiselev, Oleg Komissarov, Andrey Grudinin, Mikhail Shartukova, Maria Romanovskaya-Romanko, Ekaterina A. Kudryavets, Yuri Bezdenezhnykh, Natalya Lykhova, Oleksandra Semesyuk, Nadiia Concetti, Antonio Tsyb, Anatoly Filimonova, Marina Makarchuk, Victoria Yakubovsky, Raisa Chursov, Andrey Shcherbinina, Vita Shneider, Alexander Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding vector |
title | Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding vector |
title_full | Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding vector |
title_fullStr | Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding vector |
title_full_unstemmed | Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding vector |
title_short | Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding vector |
title_sort | broad-spectrum anti-tumor and anti-metastatic dna vaccine based on p62-encoding vector |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858567/ https://www.ncbi.nlm.nih.gov/pubmed/24121124 |
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