anti-CD11b monoclonal antibody ASD141

A monoclonal antibody directed against the CD11b (integrin alpha-M; ITGAM; integrin alpha M chain) subunit of MAC-1 (integrin alphaM/beta2; CD11b/CD18; CR3), with potential innate immune checkpoint inhibitory, immunomodulating and antineoplastic activities. Upon administration, anti-CD11b monoclonal antibody ASD141 targets, binds to and blocks the CD11b subunit of the Mac-1 receptor, thereby preventing TLT-1 (pro-T) binding to CD11b receptors on immature, innate myeloid cells in the tumor microenvironment (TME). This prevents CD11b-mediated signaling, abrogates the TLT-1-driven immunosuppressive nature of the TME and modulates the TME. This reduces infiltration of immunosuppressive tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), activates the innate immune system, and promotes infiltration of antigen-presenting cells (APCs). Specifically, the infiltration of mature interleukin-12 (IL-12)-producing dendritic cells (DCs) increases, and pro-inflammatory macrophage polarization is induced while immunosuppressive macrophage polarization is suppressed. The DC- and macrophage-driven anti-tumor immune responses along with the increase in cytotoxic T lymphocytes (CTLs) and production of interferon-gamma (IFN-g) kill tumor cells and suppress tumor growth. CD11b, a member of the integrin family of cell adhesion receptors and alpha-chain of the integrin receptor alphaMbeta2, is highly expressed on immune cells and is a negative regulator of immune suppression. TLT-1, a key regulatory protein released from platelets, plays a key role in the induction of the immune suppressive environment in the tumor and immune checkpoint blockade. Its expression in the TME is correlated with poor prognosis.