Definition

A recombinant human bispecific antibody targeting both the tumor-associated antigen (TAA) epidermal growth factor receptor (EGFR) and the costimulatory receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9), with potential checkpoint inhibitory, immunostimulating and antineoplastic activities. Upon administration, anti-EGFR/anti-4-1BB bispecific antibody HLX35 simultaneously targets and binds to the extracellular domain of EGFR, which is expressed on a variety of tumor cells and 4-1BB, which is expressed on activated T lymphocytes, natural killer (NK) cells and NK-T cells. This crosslinks EGFR-expressing tumor cells and 4-1BB-expressing T cells. The binding to EGFR inactivates EGFR and prevents EGFR-mediated signaling. Through 4-1BB binding, HLX35 acts as a conditional 4-1BB agonist, resulting in cytotoxic T-cell co-stimulation and enhances T-lymphocyte-mediated anti-tumor activity. It also activates memory T cells, NK cells and dendritic cells (DCs) in the tumor microenvironment (TME). This activates antigen-specific T lymphocytes and enhances cytotoxic T-cell-mediated lysis in EGFR-expressing tumor cells. 4-1BB, a surface glycoprotein of the tumor necrosis factor receptor superfamily, is an inducible costimulatory receptor that plays a key role in T-cell proliferation, survival and cytolytic activity. EGFR, belonging to the receptor tyrosine kinases family and upregulated or mutated in a variety of tumor cell types, plays a key role in tumor cell proliferation.