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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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.
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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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