Exploiting nature’s own defense mechanisms to eliminate target proteins or cells is an attractive therapeutic avenue. In this project we aim to leverage this therapeutic potential by developing Multivalent Immune TArgeting synthetic Chimeric therapeuticS, i.e. MITACS, which are synthetic chimeric molecules that bind to target proteins or cells and flags them for destruction by endogenous mechanisms. Focusing on an onco-immunological context, MITACS will, on the one hand, be designed to trigger killing by innate immune cells. On the other hand, MITACS will be designed to trigger lysosomal degradation of extracellular target proteins of interest or cell surface proteins on pro-tumoral cell subsets. MITACS will be evaluated in vivo in pre-clinical murine models for their ability to induce therapeutic antitumor activity. By investigating in-depth the exact role of the different immune cell subsets in the tumor microenvironment in response to MITACS treatment we aim to gather novel insights and use these to further engineer MITACS to mount immunological memory that provides long term protection against relapse and metastasis.