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Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors
BACKGROUND: DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols. We report the results of 2 multicenter phase 1 trials involving adult cancer...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599587/ https://www.ncbi.nlm.nih.gov/pubmed/23497415 http://dx.doi.org/10.1186/1479-5876-11-62 |
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author | Diaz, Claudia Marcela Chiappori, Alberto Aurisicchio, Luigi Bagchi, Ansuman Clark, Jason Dubey, Sheri Fridman, Arthur Fabregas, Jesus C Marshall, John Scarselli, Elisa La Monica, Nicola Ciliberto, Gennaro Montero, Alberto J |
author_facet | Diaz, Claudia Marcela Chiappori, Alberto Aurisicchio, Luigi Bagchi, Ansuman Clark, Jason Dubey, Sheri Fridman, Arthur Fabregas, Jesus C Marshall, John Scarselli, Elisa La Monica, Nicola Ciliberto, Gennaro Montero, Alberto J |
author_sort | Diaz, Claudia Marcela |
collection | PubMed |
description | BACKGROUND: DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols. We report the results of 2 multicenter phase 1 trials involving adult cancer patients (n=33) with stage II-IV disease. METHODS: Patients were vaccinated with V930 alone, a DNA vaccine containing equal amounts of plasmids expressing the extracellular and trans-membrane domains of human HER2, and a plasmid expressing CEA fused to the B subunit of Escherichia coli heat labile toxin (Study 1), or a heterologous prime-boost vaccination approach with V930 followed by V932, a dicistronic adenovirus subtype-6 viral vector vaccine coding for the same antigens (Study 2). RESULTS: The use of the V930 vaccination with electroporation alone or in combination with V932 was well-tolerated without any serious adverse events. In both studies, the most common vaccine-related side effects were injection site reactions and arthralgias. No measurable cell-mediated immune response (CMI) to CEA or HER2 was detected in patients by ELISPOT; however, a significant increase of both cell-mediated immunity and antibody titer against the bacterial heat labile toxin were observed upon vaccination. CONCLUSION: V930 vaccination alone or in combination with V932 was well tolerated without any vaccine-related serious adverse effects, and was able to induce measurable immune responses against bacterial antigen. However, the prime-boost strategy did not appear to augment any detectable CMI responses against either CEA or HER2. TRIAL REGISTRATION: Study 1 – ClinicalTrials.gov, NCT00250419; Study 2 – ClinicalTrials.gov, NCT00647114. |
format | Online Article Text |
id | pubmed-3599587 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35995872013-03-17 Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors Diaz, Claudia Marcela Chiappori, Alberto Aurisicchio, Luigi Bagchi, Ansuman Clark, Jason Dubey, Sheri Fridman, Arthur Fabregas, Jesus C Marshall, John Scarselli, Elisa La Monica, Nicola Ciliberto, Gennaro Montero, Alberto J J Transl Med Research BACKGROUND: DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols. We report the results of 2 multicenter phase 1 trials involving adult cancer patients (n=33) with stage II-IV disease. METHODS: Patients were vaccinated with V930 alone, a DNA vaccine containing equal amounts of plasmids expressing the extracellular and trans-membrane domains of human HER2, and a plasmid expressing CEA fused to the B subunit of Escherichia coli heat labile toxin (Study 1), or a heterologous prime-boost vaccination approach with V930 followed by V932, a dicistronic adenovirus subtype-6 viral vector vaccine coding for the same antigens (Study 2). RESULTS: The use of the V930 vaccination with electroporation alone or in combination with V932 was well-tolerated without any serious adverse events. In both studies, the most common vaccine-related side effects were injection site reactions and arthralgias. No measurable cell-mediated immune response (CMI) to CEA or HER2 was detected in patients by ELISPOT; however, a significant increase of both cell-mediated immunity and antibody titer against the bacterial heat labile toxin were observed upon vaccination. CONCLUSION: V930 vaccination alone or in combination with V932 was well tolerated without any vaccine-related serious adverse effects, and was able to induce measurable immune responses against bacterial antigen. However, the prime-boost strategy did not appear to augment any detectable CMI responses against either CEA or HER2. TRIAL REGISTRATION: Study 1 – ClinicalTrials.gov, NCT00250419; Study 2 – ClinicalTrials.gov, NCT00647114. BioMed Central 2013-03-08 /pmc/articles/PMC3599587/ /pubmed/23497415 http://dx.doi.org/10.1186/1479-5876-11-62 Text en Copyright © 2013 Diaz et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Diaz, Claudia Marcela Chiappori, Alberto Aurisicchio, Luigi Bagchi, Ansuman Clark, Jason Dubey, Sheri Fridman, Arthur Fabregas, Jesus C Marshall, John Scarselli, Elisa La Monica, Nicola Ciliberto, Gennaro Montero, Alberto J Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors |
title | Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors |
title_full | Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors |
title_fullStr | Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors |
title_full_unstemmed | Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors |
title_short | Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors |
title_sort | phase 1 studies of the safety and immunogenicity of electroporated her2/cea dna vaccine followed by adenoviral boost immunization in patients with solid tumors |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599587/ https://www.ncbi.nlm.nih.gov/pubmed/23497415 http://dx.doi.org/10.1186/1479-5876-11-62 |
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