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A general strategy to optimize immunogenicity of HLA-B*0702 restricted cryptic peptides from tumor associated antigens: Design of universal neo-antigen like tumor vaccines for HLA-B*0702 positive patients
Tumor Associated Antigens (TAAs) are the privileged targets of almost all the cancer vaccines tested to date. Unfortunately all these vaccines failed to show a clinical efficacy. The main reason for this failure is the immune tolerance to TAAs that are self-proteins expressed by normal and cancer ce...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312321/ https://www.ncbi.nlm.nih.gov/pubmed/27506946 http://dx.doi.org/10.18632/oncotarget.11086 |
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author | Gallou, Catherine Rougeot, Aude Graff-Dubois, Stéphanie Kosmatopoulos, Kostas Menez-Jamet, Jeanne |
author_facet | Gallou, Catherine Rougeot, Aude Graff-Dubois, Stéphanie Kosmatopoulos, Kostas Menez-Jamet, Jeanne |
author_sort | Gallou, Catherine |
collection | PubMed |
description | Tumor Associated Antigens (TAAs) are the privileged targets of almost all the cancer vaccines tested to date. Unfortunately all these vaccines failed to show a clinical efficacy. The main reason for this failure is the immune tolerance to TAAs that are self-proteins expressed by normal and cancer cells. Self-tolerance to TAAs is directed against their dominant rather than against their cryptic epitopes. The best way to overcome self-tolerance to TAAs would therefore be to target their cryptic epitopes. However, because of their low HLA-I affinity, cryptic peptides are non-immunogenic and cannot be used to stimulate an antitumor immune response unless their immunogenicity has been previously enhanced. In this paper we describe a general approach to enhance immunogenicity of almost all the HLA-B*0702 restricted cryptic peptides derived from TAAs. It consists in substituting residues at position 1 or 9 of low HLA-B*0702 affinity cryptic peptides by an Alanine or a Leucine respectively. These substitutions increase affinity of peptides for HLA-B*0702. These optimized cryptic peptides are strongly immunogenic and very importantly CTL they stimulate recognize their native counterparts. TAAs derived optimized cryptic peptides can be considered as universal antitumor vaccine since they escape self-tolerance, are immunogenic and are not patient specific. |
format | Online Article Text |
id | pubmed-5312321 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53123212017-03-06 A general strategy to optimize immunogenicity of HLA-B*0702 restricted cryptic peptides from tumor associated antigens: Design of universal neo-antigen like tumor vaccines for HLA-B*0702 positive patients Gallou, Catherine Rougeot, Aude Graff-Dubois, Stéphanie Kosmatopoulos, Kostas Menez-Jamet, Jeanne Oncotarget Research Paper Tumor Associated Antigens (TAAs) are the privileged targets of almost all the cancer vaccines tested to date. Unfortunately all these vaccines failed to show a clinical efficacy. The main reason for this failure is the immune tolerance to TAAs that are self-proteins expressed by normal and cancer cells. Self-tolerance to TAAs is directed against their dominant rather than against their cryptic epitopes. The best way to overcome self-tolerance to TAAs would therefore be to target their cryptic epitopes. However, because of their low HLA-I affinity, cryptic peptides are non-immunogenic and cannot be used to stimulate an antitumor immune response unless their immunogenicity has been previously enhanced. In this paper we describe a general approach to enhance immunogenicity of almost all the HLA-B*0702 restricted cryptic peptides derived from TAAs. It consists in substituting residues at position 1 or 9 of low HLA-B*0702 affinity cryptic peptides by an Alanine or a Leucine respectively. These substitutions increase affinity of peptides for HLA-B*0702. These optimized cryptic peptides are strongly immunogenic and very importantly CTL they stimulate recognize their native counterparts. TAAs derived optimized cryptic peptides can be considered as universal antitumor vaccine since they escape self-tolerance, are immunogenic and are not patient specific. Impact Journals LLC 2016-08-05 /pmc/articles/PMC5312321/ /pubmed/27506946 http://dx.doi.org/10.18632/oncotarget.11086 Text en Copyright: © 2016 Gallou 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 Gallou, Catherine Rougeot, Aude Graff-Dubois, Stéphanie Kosmatopoulos, Kostas Menez-Jamet, Jeanne A general strategy to optimize immunogenicity of HLA-B*0702 restricted cryptic peptides from tumor associated antigens: Design of universal neo-antigen like tumor vaccines for HLA-B*0702 positive patients |
title | A general strategy to optimize immunogenicity of HLA-B*0702 restricted cryptic peptides from tumor associated antigens: Design of universal neo-antigen like tumor vaccines for HLA-B*0702 positive patients |
title_full | A general strategy to optimize immunogenicity of HLA-B*0702 restricted cryptic peptides from tumor associated antigens: Design of universal neo-antigen like tumor vaccines for HLA-B*0702 positive patients |
title_fullStr | A general strategy to optimize immunogenicity of HLA-B*0702 restricted cryptic peptides from tumor associated antigens: Design of universal neo-antigen like tumor vaccines for HLA-B*0702 positive patients |
title_full_unstemmed | A general strategy to optimize immunogenicity of HLA-B*0702 restricted cryptic peptides from tumor associated antigens: Design of universal neo-antigen like tumor vaccines for HLA-B*0702 positive patients |
title_short | A general strategy to optimize immunogenicity of HLA-B*0702 restricted cryptic peptides from tumor associated antigens: Design of universal neo-antigen like tumor vaccines for HLA-B*0702 positive patients |
title_sort | general strategy to optimize immunogenicity of hla-b*0702 restricted cryptic peptides from tumor associated antigens: design of universal neo-antigen like tumor vaccines for hla-b*0702 positive patients |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312321/ https://www.ncbi.nlm.nih.gov/pubmed/27506946 http://dx.doi.org/10.18632/oncotarget.11086 |
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