A humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting sialic acid binding Ig-like lectin 15 (Siglec-15; SIGLEC15; S15), a member of the sialic acid-binding immunoglobulin type lectins, with potential antineoplastic and immunomodulatory activities. Upon administration, anti-S15 monoclonal antibody NC318 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, inhibition of T-cell responses, and stimulation of tumor angiogenesis and disease progression. S15, a highly conserved type 1 cell surface protein, normally involved in osteoclast differentiation and bone remodeling, may play a role in the survival and differentiation of TAMs.