monomethyl-auristatin-e and Esophageal-Squamous-Cell-Carcinoma

Epidermal growth factor receptor (EGFR) is a rational target for cancer therapy, because its overexpression plays an important oncogenic role in a variety of solid tumors; however, EGFR-targeted antibody-drug conjugate (ADC) therapy for esophageal squamous cell carcinoma (ESCC) is exceedingly rare. LR004 is a novel anti-EGFR antibody with the advantages of improved safety and fewer hypersensitivity reactions. It may be of great value as a carrier in ADCs with high binding affinity and internalization ability. Here, we prepared an EGFR-targeting ADC, LR004-VC-MMAE, and evaluated its antitumor activities against ESCC and EGFR-positive cells. LR004 was covalently conjugated with monomethyl auristatin E (MMAE) via a VC linker by antibody interchain disulfide bond reduction. VC-MMAE was conjugated with LR004 with approximately 4.0 MMAE molecules per ADC. LR004-VC-MMAE showed a potent antitumor effect against ESCC and other EGFR-positive cells with IC

Topics: Animals; Antibodies, Monoclonal; Cell Death; Cell Line, Tumor; Endocytosis; ErbB Receptors; Esophageal Squamous Cell Carcinoma; Female; Humans; Immunoconjugates; Inhibitory Concentration 50; Mice, Inbred BALB C; Mice, Nude; Oligopeptides; Treatment Outcome; Xenograft Model Antitumor Assays