Anti-Human HER3 antibody (Elge

Elgemtumab(LJM716) 是一种全人IgG 单克隆抗体。Elgemtumab 可特异性结合 HER3，阻断配体依赖性和非依赖性 HER3 信号转导和细胞增殖，具有良好的抗肿瘤潜力。

Elgemtumab (LJM716) is a fully human IgG monoclonal antibody that specifically targets HER3, inhibiting both ligand-dependent and independent HER3 signal transduction and cell proliferation. This function showcases its significant anti-tumor capabilities.

anti-HER3 monoclonal antibody LJM716
A human monoclonal antibody directed against the human epidermal growth factor receptor HER3 (ErbB3) with potential antineoplastic activity. Anti-HER3 monoclonal antibody LJM716 possesses a novel mechanism of action; LJM716 binds to and locks HER3 in the inactive conformation and does not interfere with its interaction with neuregulin (NRG). The inactivated form of HER3 blocks the PI3K/Akt signaling pathway, thereby inhibiting cellular proliferation in HER2 or NRG expressing tumor cells. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in tumors; it has no active kinase domain but is activated through heterodimerization with other members of the EGFR receptor family, such as HER2.

HER3 is a unique EGFR family member with no or little intracellular tyrosine kinase activity. Compared with the other EGFR family members, HER3 diverges at critical residues in the kinase domain locking it in an inactive-like conformation . Although HER3 has been reported to have some kinase activity, it is suggested to be 1000-fold weaker than the kinase activity of the fully activated EGFR . Since HER3 is unable to form homodimers, its activation depends on heterodimerization with another receptor in order to induce the downstream C-terminal phosphorylation events .

The HER3 gene localizes in the long arm of chromosome 12 (12q13.2), encoding a 180 kDa protein . The extracellular domain of HER3 is divided into four subdomains (I–IV): subdomains I and III are leucine-rich β-helical areas responsible for the ligand binding, whereas subdomains II and IV are cysteine-rich regions. Subdomain II also contains a dimerization arm necessary for the interaction with other receptors. The transmembrane domain is followed by an intracellular domain enclosing a flexible juxtamembrane region, kinase domain, and the C-terminal tail. In absence of a ligand, binding between subdomains II and IV keeps HER3 in an inactive state . Upon ligand binding, the dimerization partner’s kinase domain trans-phosphorylates the tyrosine residues in the C-terminal tail of HER3 .

Upon ligand binding, HER3 preferentially dimerizes with EGFR or HER2 inducing a conformational change in the receptor pair. The conformational change leads into transphosphorylation event in the intracellular kinase tail, where the C-terminal tail of HER3 acts as an acceptor for multiple phosphorylations. This induces activation of signaling cascades promoting cell survival and proliferation. EGFR: Epidermal growth factor receptor, EGF: Epidermal growth factor, HER2: Human epidermal growth factor receptor 2, HER3: Human epidermal growth factor receptor 3, NRG: Neuregulin, p85: 85kDa regulator subunit of phosphoinositide 3-kinase, p110: 110kDa catalytic subunit of phosphoinositide 3-kinase, AKT: protein kinase B, SHC: SHC-transforming protein 1, GRB2: growth factor receptor bound protein 2, SOS: Son of sevenless, RAS: RAS GTPase, RAF: Raf kinase, MAPK: Mitogen-activated protein kinase.

HER3 is a unique EGFR family member with no or little intracellular tyrosine kinase activity. Compared with the other EGFR family members, HER3 diverges at critical residues in the kinase domain locking it in an inactive-like conformation . Although HER3 has been reported to have some kinase activity, it is suggested to be 1000-fold weaker than the kinase activity of the fully activated EGFR . Since HER3 is unable to form homodimers, its activation depends on heterodimerization with another receptor in order to induce the downstream C-terminal phosphorylation events .

The HER3 gene localizes in the long arm of chromosome 12 (12q13.2), encoding a 180 kDa protein . The extracellular domain of HER3 is divided into four subdomains (I–IV): subdomains I and III are leucine-rich β-helical areas responsible for the ligand binding, whereas subdomains II and IV are cysteine-rich regions. Subdomain II also contains a dimerization arm necessary for the interaction with other receptors. The transmembrane domain is followed by an intracellular domain enclosing a flexible juxtamembrane region, kinase domain, and the C-terminal tail. In absence of a ligand, binding between subdomains II and IV keeps HER3 in an inactive state . Upon ligand binding, the dimerization partner’s kinase domain trans-phosphorylates the tyrosine residues in the C-terminal tail of HER3 .

Upon ligand binding, HER3 preferentially dimerizes with EGFR or HER2 inducing a conformational change in the receptor pair. The conformational change leads into transphosphorylation event in the intracellular kinase tail, where the C-terminal tail of HER3 acts as an acceptor for multiple phosphorylations. This induces activation of signaling cascades promoting cell survival and proliferation. EGFR: Epidermal growth factor receptor, EGF: Epidermal growth factor, HER2: Human epidermal growth factor receptor 2, HER3: Human epidermal growth factor receptor 3, NRG: Neuregulin, p85: 85kDa regulator subunit of phosphoinositide 3-kinase, p110: 110kDa catalytic subunit of phosphoinositide 3-kinase, AKT: protein kinase B, SHC: SHC-transforming protein 1, GRB2: growth factor receptor bound protein 2, SOS: Son of sevenless, RAS: RAS GTPase, RAF: Raf kinase, MAPK: Mitogen-activated protein kinase.