Oncotarget

Research Papers:

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

Catherine Gallou, Aude Rougeot, Stéphanie Graff-Dubois, Kostas Kosmatopoulos and Jeanne Menez-Jamet _

PDF  |  HTML  |  How to cite

Oncotarget. 2016; 7:59417-59428. https://doi.org/10.18632/oncotarget.11086

Metrics: PDF 1881 views  |   HTML 2380 views  |   ?  


Abstract

Catherine Gallou1, Aude Rougeot1, Stéphanie Graff-Dubois2, Kostas Kosmatopoulos1, Jeanne Menez-Jamet1

1Vaxon Biotech, 75015, Paris, France

2University Pierre-and-Marie-Curie (aka University Paris 06), INSERM U1135, CNRS ERL8255, 75013, Paris, France

Correspondence to:

Jeanne Menez-Jamet, email: [email protected]

Keywords: HLA-B7, vaccination, immunotherapy, optimized, cryptic

Received: May 27, 2016     Accepted: July 13, 2016     Published: August 05, 2016

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 11086