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Synthetic integrin-binding immune stimulators target cancer cells and prevent tumor formation.

Synthetic integrin-binding immune stimulators target cancer cells and prevent tumor formation.
Author Information (click to view)

Brehs M, Pötgens AJG, Steitz J, Thewes K, Schwarz J, Conibear AC, Bartneck M, Tacke F, Becker CFW,


Brehs M, Pötgens AJG, Steitz J, Thewes K, Schwarz J, Conibear AC, Bartneck M, Tacke F, Becker CFW, (click to view)

Brehs M, Pötgens AJG, Steitz J, Thewes K, Schwarz J, Conibear AC, Bartneck M, Tacke F, Becker CFW,

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Scientific reports 2017 12 147(1) 17592 doi 10.1038/s41598-017-17627-0
Abstract

Immuno-oncology approaches mainly utilize monoclonal antibodies or protein-based scaffolds that bind with high affinity to cancer cells and can generate an immune response. Peptides can also bind with high affinity to cancer cells and are intermediate in size between antibodies and small molecules. They are also synthetically accessible and therefore easily modified to optimize their stability, binding affinity and selectivity. Here we describe the design of immune system engagers (ISErs), a novel class of synthetic peptide-based compounds that bind specifically to cancer cells and stimulate the immune system. A prototype, Y9, targets integrin α3, which is overexpressed on several cancer cells, and activates the immune system via a formyl methionine-containing effector peptide. Injection of Y9 leads to immune cell infiltration into tissue and prevents tumor formation in a guinea pig model. The anti-tumor activity and synthetic accessibility of Y9 illustrate that ISErs could be applied to a wide variety of targets and diseases.

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