Definition

A humanized monoclonal antibody targeting the immune checkpoint molecule sialic acid-binding immunoglobulin (Ig)-like lectin 15 (Siglec-15; SIGLEC15; S15; CD33L3), with potential immune checkpoint inhibitory, antineoplastic and immunomodulatory activities. Upon administration, anti-S15 monoclonal antibody PYX-106 targets and binds to S15 on the surface of tumor-associated macrophages (TAMs) and certain tumor cells. Binding to S15 may disrupt TAM-mediated activities such as promotion of tumor initiation and metastasis of tumor cells and inhibition of CD8-positive and CD4-positive T-cell responses. This leads to activation of the immune system and an inhibition of tumor cell growth. S15, a highly conserved type 1 cell surface protein, normally involved in osteoclast differentiation and bone remodeling, is overexpressed on and may play a key role in the survival and differentiation of TAMs and various tumor cells.