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Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T...

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Autores principales: Chai, San Jiun, Yap, Yoke Yeow, Foo, Yoke Ching, Yap, Lee Fah, Ponniah, Sathibalan, Teo, Soo Hwang, Cheong, Sok Ching, Patel, Vyomesh, Lim, Kue Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633155/
https://www.ncbi.nlm.nih.gov/pubmed/26536470
http://dx.doi.org/10.1371/journal.pone.0130464
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author Chai, San Jiun
Yap, Yoke Yeow
Foo, Yoke Ching
Yap, Lee Fah
Ponniah, Sathibalan
Teo, Soo Hwang
Cheong, Sok Ching
Patel, Vyomesh
Lim, Kue Peng
author_facet Chai, San Jiun
Yap, Yoke Yeow
Foo, Yoke Ching
Yap, Lee Fah
Ponniah, Sathibalan
Teo, Soo Hwang
Cheong, Sok Ching
Patel, Vyomesh
Lim, Kue Peng
author_sort Chai, San Jiun
collection PubMed
description Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9–20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients.
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spelling pubmed-46331552015-11-13 Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma Chai, San Jiun Yap, Yoke Yeow Foo, Yoke Ching Yap, Lee Fah Ponniah, Sathibalan Teo, Soo Hwang Cheong, Sok Ching Patel, Vyomesh Lim, Kue Peng PLoS One Research Article Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9–20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients. Public Library of Science 2015-11-04 /pmc/articles/PMC4633155/ /pubmed/26536470 http://dx.doi.org/10.1371/journal.pone.0130464 Text en © 2015 Chai et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Chai, San Jiun
Yap, Yoke Yeow
Foo, Yoke Ching
Yap, Lee Fah
Ponniah, Sathibalan
Teo, Soo Hwang
Cheong, Sok Ching
Patel, Vyomesh
Lim, Kue Peng
Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma
title Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma
title_full Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma
title_fullStr Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma
title_full_unstemmed Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma
title_short Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma
title_sort identification of four-jointed box 1 (fjx1)-specific peptides for immunotherapy of nasopharyngeal carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633155/
https://www.ncbi.nlm.nih.gov/pubmed/26536470
http://dx.doi.org/10.1371/journal.pone.0130464
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