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Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects
Tumor-associated carbohydrate antigens (TACAs) support cell survival that could be interrupted by anti-TACA antibodies. Among TACAs that mediate cell survival signals are the neolactoseries antigen Lewis Y (LeY) and the ganglioside GD2. To induce sustained immunity against both LeY and GD2, we devel...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716801/ https://www.ncbi.nlm.nih.gov/pubmed/29228761 http://dx.doi.org/10.18632/oncotarget.21959 |
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author | Hutchins, Laura F. Makhoul, Issam Emanuel, Peter D. Pennisi, Angela Siegel, Eric R. Jousheghany, Fariba Guo, Xueyan Pashov, Anastas D. Monzavi-Karbassi, Behjatolah Kieber-Emmons, Thomas |
author_facet | Hutchins, Laura F. Makhoul, Issam Emanuel, Peter D. Pennisi, Angela Siegel, Eric R. Jousheghany, Fariba Guo, Xueyan Pashov, Anastas D. Monzavi-Karbassi, Behjatolah Kieber-Emmons, Thomas |
author_sort | Hutchins, Laura F. |
collection | PubMed |
description | Tumor-associated carbohydrate antigens (TACAs) support cell survival that could be interrupted by anti-TACA antibodies. Among TACAs that mediate cell survival signals are the neolactoseries antigen Lewis Y (LeY) and the ganglioside GD2. To induce sustained immunity against both LeY and GD2, we developed a carbohydrate mimicking peptide (CMP) as a surrogate pan-immunogen that mimics both. This CMP, referred to as P10s, is the N-terminal half of a peptide vaccine named P10s-PADRE, the C-terminal half of which (PADRE) is a Pan-T-cell epitope. A Phase I dose-escalation trial of P10s-PADRE plus adjuvant MONTANIDE™ ISA 51 VG was conducted in subjects with metastatic breast cancer to test 300 and 500 μg/injection in two cohorts of 3 subjects each. Doses of the P10s-PADRE vaccine were administered to research participants subcutaneously on weeks 1, 2, 3, 7 and 19. Antibody responses to P10s, GD2, and LeY were measured by ELISA. The P10s-PADRE vaccine induced antibodies specifically reactive with P10s, LeY and GD2 in all 6 subjects. Serum antibodies displayed Caspase-3-dependent apoptotic functionality against LeY or GD2 expressing breast cancer cell lines. Immunization with the P10s-PADRE vaccine was well-tolerated and induced functional antibodies, and the data suggest potential clinical benefit. |
format | Online Article Text |
id | pubmed-5716801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57168012017-12-08 Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects Hutchins, Laura F. Makhoul, Issam Emanuel, Peter D. Pennisi, Angela Siegel, Eric R. Jousheghany, Fariba Guo, Xueyan Pashov, Anastas D. Monzavi-Karbassi, Behjatolah Kieber-Emmons, Thomas Oncotarget Clinical Research Paper Tumor-associated carbohydrate antigens (TACAs) support cell survival that could be interrupted by anti-TACA antibodies. Among TACAs that mediate cell survival signals are the neolactoseries antigen Lewis Y (LeY) and the ganglioside GD2. To induce sustained immunity against both LeY and GD2, we developed a carbohydrate mimicking peptide (CMP) as a surrogate pan-immunogen that mimics both. This CMP, referred to as P10s, is the N-terminal half of a peptide vaccine named P10s-PADRE, the C-terminal half of which (PADRE) is a Pan-T-cell epitope. A Phase I dose-escalation trial of P10s-PADRE plus adjuvant MONTANIDE™ ISA 51 VG was conducted in subjects with metastatic breast cancer to test 300 and 500 μg/injection in two cohorts of 3 subjects each. Doses of the P10s-PADRE vaccine were administered to research participants subcutaneously on weeks 1, 2, 3, 7 and 19. Antibody responses to P10s, GD2, and LeY were measured by ELISA. The P10s-PADRE vaccine induced antibodies specifically reactive with P10s, LeY and GD2 in all 6 subjects. Serum antibodies displayed Caspase-3-dependent apoptotic functionality against LeY or GD2 expressing breast cancer cell lines. Immunization with the P10s-PADRE vaccine was well-tolerated and induced functional antibodies, and the data suggest potential clinical benefit. Impact Journals LLC 2017-10-23 /pmc/articles/PMC5716801/ /pubmed/29228761 http://dx.doi.org/10.18632/oncotarget.21959 Text en Copyright: © 2017 Hutchins et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Clinical Research Paper Hutchins, Laura F. Makhoul, Issam Emanuel, Peter D. Pennisi, Angela Siegel, Eric R. Jousheghany, Fariba Guo, Xueyan Pashov, Anastas D. Monzavi-Karbassi, Behjatolah Kieber-Emmons, Thomas Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects |
title | Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects |
title_full | Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects |
title_fullStr | Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects |
title_full_unstemmed | Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects |
title_short | Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects |
title_sort | targeting tumor-associated carbohydrate antigens: a phase i study of a carbohydrate mimetic-peptide vaccine in stage iv breast cancer subjects |
topic | Clinical Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716801/ https://www.ncbi.nlm.nih.gov/pubmed/29228761 http://dx.doi.org/10.18632/oncotarget.21959 |
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