The high-affinity binding of monoclonal antibodies or other protein-based scaffolds to cancer cells has been coupled with the stimulation of an adaptive immune response in several successful immuno-oncology approaches. Peptides can also bind with high affinity to cancer cells and are intermediate in size between antibodies and small molecules. Here we describe the design, synthesis and application of a fully synthetic immune system engager (ISEr) that mimics the functions of an antibody by binding specifically to cancer cells and stimulating the immune system. In the prototype ‘Y9’, two ‘binder’ peptides target integrin α3, which is overexpressed on many cancer cell types, and a formyl methionine-containing ‘effector’ activates the innate immune system. Furthermore, injection of Y9 led to immune cell infiltration and prevented tumor formation in a guinea pig model. The multifunctional construct is assembled by solid phase peptide synthesis with the cancer-targeting and immune-stimulating peptides linked via monodisperse PEG-based polymers. Chemical synthesis allows for versatility in the combination of ‘binder’ and ‘effector’ peptides and also provides the possibility for attaching labels or ligation handles for imaging and chemoselective ligations. The anti-tumor activity and synthetic accessibility of ISErs demonstrate that these novel compounds could be applied to a wide variety of cancer cell targets as well as towards other diseases with such specific markers.