anti-TREM1 agonistic monoclonal antibody PY159

A humanized agonistic monoclonal antibody targeting triggering receptor expressed on myeloid cells 1 (TREM1), with potential immunomodulating and antineoplastic activities. Upon administration, anti-TREM1 agonistic monoclonal antibody PY159 targets, binds to, crosslinks and activates TREM1 located on immunosuppressive tumor-associated myeloid cells within the tumor microenvironment (TME), including monocytic myeloid derived suppressor cells (mMDSCs), tumor associated neutrophils (TANs), and tumor associated macrophages (TAMs). This activates TREM1-mediated signaling through the TREM1/DNAX activating protein of 12kDa (DAP12) complex. This reprograms and repolarizes the immunosuppressive myeloid cells, thereby inducing a pro-inflammatory state in these cells and altering the TME. This stimulates anti-tumor immune responses leading to tumor cell destruction. TREM1, an immunoglobulin (Ig) superfamily transmembrane protein constitutively expressed on the cell surface of peripheral blood monocytes and neutrophils, is expressed within the TME and is associated with poorer patient outcomes. Activation of TREM1 may amplify immune responses.