title: Combination of novel HER2-targeting antibody 1E11 with trastuzumab shows synergistic antitumor activity in HER2-positive gastric cancer.
abstract: The synergistic interaction of two antibodies targeting the same protein could be developed as an effective anti-cancer therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast and gastric cancer patients, and HER2-targeted antibody therapy using trastuzumab is effective in many of these patients. Nonetheless, improving therapeutic efficacy and patient survival is important, particularly in patients with HER2-positive gastric cancer. Here, we describe the development of 1E11, a HER2-targeted humanized monoclonal antibody showing increased efficacy in a highly synergistic manner in combination with trastuzumab in the HER2-overexpressing gastric cancer cell lines NCI-N87 and OE-19. The two antibodies bind to sub-domain IV of the receptor, but have non-overlapping epitopes, allowing them to simultaneously bind HER2. Treatment with 1E11 alone induced apoptosis in HER2-positive cancer cells, and this effect was enhanced by combination treatment with trastuzumab. Combination treatment with 1E11 and trastuzumab reduced the levels of total HER2 protein and those of aberrant HER2 signaling molecules including phosphorylated HER3 and EGFR. The synergistic antitumor activity of 1E11 in combination with trastuzumab indicates that it could be a novel potent therapeutic antibody for the treatment of HER2-overexpressing gastric cancers.
authors.affiliation: AbClon Inc., #1403, Ace Twin Tower 1, 212-1, Guro-dong, Guro-gu, Seoul 152-779, Republic of Korea; School of Biological Sciences, Seoul National University, Seoul 152-747, Republic of Korea.
authors.forename: Bong-Kook
authors.initials: BK
authors.lastname: Ko
authors.affiliation: AbClon Inc., #1403, Ace Twin Tower 1, 212-1, Guro-dong, Guro-gu, Seoul 152-779, Republic of Korea.
authors.forename: Sook-Yeon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: AbClon Inc., #1403, Ace Twin Tower 1, 212-1, Guro-dong, Guro-gu, Seoul 152-779, Republic of Korea.
authors.forename: Young-Ha
authors.initials: YH
authors.lastname: Lee
authors.affiliation: AbClon Inc., #1403, Ace Twin Tower 1, 212-1, Guro-dong, Guro-gu, Seoul 152-779, Republic of Korea.
authors.forename: In-Sik
authors.initials: IS
authors.lastname: Hwang
authors.affiliation: Department of Immunotechnology, Lund University, Medicon Village, Lund, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Persson
authors.affiliation: School of Biotechnology, KTH Royal Institute of Technology, SE-106 91 Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Rockberg
authors.affiliation: Department of Immunotechnology, Lund University, Medicon Village, Lund, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Borrebaeck
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 152-747, Republic of Korea.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Park
authors.affiliation: AbClon Inc., #1403, Ace Twin Tower 1, 212-1, Guro-dong, Guro-gu, Seoul 152-779, Republic of Korea. Electronic address: ktkim@abclon.com.
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Kim
authors.affiliation: School of Biotechnology, KTH Royal Institute of Technology, SE-106 91 Stockholm, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlen
authors.affiliation: AbClon Inc., #1403, Ace Twin Tower 1, 212-1, Guro-dong, Guro-gu, Seoul 152-779, Republic of Korea.
authors.forename: Jong-Seo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: 1E11; Combination; Gastric cancer; HER2; Synergism; Trastuzumab