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Targeting inhibition of Foxp3 by a CD28 2′-Fluro oligonucleotide aptamer conjugated to P60-peptide enhances active cancer immunotherapy

Paper ID Volume ID Publish Year Pages File Format Full-Text
5449 385 2016 8 PDF Available
Title
Targeting inhibition of Foxp3 by a CD28 2′-Fluro oligonucleotide aptamer conjugated to P60-peptide enhances active cancer immunotherapy
Abstract

The specific inhibition of Treg function has long been a major technical challenge in cancer immunotherapy. So far no single cell-surface marker has been identified that could be used to distinguish Treg cells from other lymphocytes. The only available specific marker mostly expressed in Treg is Foxp3, which is an intracellular transcription factor. A targeting molecule able to penetrate the membrane and inhibit Foxp3 within the cell is needed. P60-peptide is able to do that, but due to lack of target specificity, the doses are extremely high. In this study we have shown as a proof of concept that P60 Foxp3 inhibitor peptide can be conjugated with a CD28 targeting aptamer to deliver the peptide to CD28-expressing cells. The AptCD28-P60 construct is a clinically feasible reagent that improves the efficacy of the unconjugated P60 peptide very significantly. This approach was used to inhibit Treg function in a vaccination context, and it has shown a significant improvement in the induced immune response, entailing a lower tumor load in an antigen-specific cancer vaccine protocol.

Keywords
Aptamer; Therapeutic; Immunotherapy; FOXP3; Treg
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Targeting inhibition of Foxp3 by a CD28 2′-Fluro oligonucleotide aptamer conjugated to P60-peptide enhances active cancer immunotherapy
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 91, June 2016, Pages 73–80
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us