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.