Therapeutic targeting of FOXP3-positive regulatory T cells using a FOXP3 peptide vaccine WO2008081581.
BACKGROUND
CD4(+)CD25(+) regulatory T cells (Tregs) regulate immunotolerance. Treg depletion causes autoimmune disease, whereas Treg expansion can prevent effective immunosurveillance of 'non-self' antigens in many clinical settings, including cancer.


OBJECTIVE
Patent WO2008081581 presents an invention to target Tregs therapeutically via vaccination with immunogenic peptides from the forkhead box P3 (FOXP3) transcription factor. Our objective was the scientific evaluation of this patent and advantages versus potential risks of this therapeutic strategy.


METHODS
There are 432 patents on Tregs and a diverse array of approaches for their therapeutic targeting; these have already been reviewed elsewhere. This article focuses on the utility of the selected peptides for specifically targeting FOXP3, whether FOXP3 expression is Treg specific and the likely effectiveness versus risk of autoimmunity relating to FOXP3-targeted immunotherapy.


CONCLUSIONS
Our analysis of the immunogenic FOXP3 peptides found many (10/21) with significant (i.e. only one or two amino-acid differences) or complete identity with other proteins; these are not suitable for specific FOXP3 targeting. Some peptides have the ability to target specific FOXP3 isoforms. FOXP3 vaccination might be an effective method for reducing Treg numbers in cancer patients. However, this must be balanced against the risks of developing autoimmunity and targeting effector T cells.
Banham
Alison H
AH
University of Oxford, John Radcliffe Hospital, Nuffield Department of Clinical Laboratory Sciences, Headington, Oxford, UK. alison.banham@ndcls.ox.ac.uk
Pulford
Karen
K
D000818:Animals; D016503:Drug Delivery Systems; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D010330:Patents as Topic; D020033:Protein Isoforms; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020033:Protein Isoforms; D014612:Vaccines