title: Therapeutic effect of anti CEACAM6 monoclonal antibody against lung adenocarcinoma by enhancing anoikis sensitivity.
abstract: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays a crucial role in tumorigenesis of lung cancer. However, the therapeutic potential for anti CEACAM6 monoclonal antibody (mAb) has only been limitedly explored. Here, we evaluate the therapeutic potential of naked anti CEACAM6 mAb against lung adenocarcinoma. Clone 8F5, recognizing B domain of CEACAM6, is established by immunizing A549 cells and screening for clones double positive for A549 and CEACAM6-Fc recombinant protein. We found that 85.7% of 70 resected lung adenocarcinoma tissue sections were positive for CEACAM6, whereas all squamous cell carcinoma examined were negative. A549 cells with high levels of CEACAM6 demonstrated more aggressive growth nature and showed increased paclitaxel chemosensitivity upon 8F5 binding. Treatment with 8F5 to A549 decreased cellular CEACAM6 expression and reversed anoikis resistance. 8F5 also decreased cellular status of Akt phosphorylation and increased apoptosis via caspase activation. In a mouse model of lung adenocarcinoma with xenotransplanted A549 cells, 8F5 treatment alone demonstrated 40% tumor growth inhibition. When combined with paclitaxel treatment, 8F5 markedly enhanced tumor growth inhibition, up to 80%. In summary, we demonstrate that anti CEACAM6 mAb is an effective therapeutic treatment for lung adenocarcinoma whose effect is further enhanced by combined treatment with paclitaxel.
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute of DiNonA Inc., Seoul, 138-736, Republic of Korea.
authors.forename: Kwon Pyo
authors.initials: KP
authors.lastname: Hong
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute of DiNonA Inc., Seoul, 138-736, Republic of Korea.
authors.forename: Mi Hyang
authors.initials: MH
authors.lastname: Shin
authors.affiliation: Research Institute of DiNonA Inc., Seoul, 138-736, Republic of Korea.
authors.forename: SangSoon
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute of DiNonA Inc., Seoul, 138-736, Republic of Korea.
authors.forename: Gil Yong
authors.initials: GY
authors.lastname: Ji
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute of DiNonA Inc., Seoul, 138-736, Republic of Korea.
authors.forename: Yoo Ri
authors.initials: YR
authors.lastname: Moon
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Ok-Jun
authors.initials: OJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Song-Yi
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Yong-Moon
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Koo
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Ho-Chang
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Seung Ryul
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Ki Hyeong
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Hye-Suk
authors.initials: HS
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Kang Hyeon
authors.initials: KH
authors.lastname: Choe
authors.affiliation: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Ki Man
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Jong-Myeon
authors.initials: JM
authors.lastname: Hong
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Si-Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Yi
authors.affiliation: Laboratory Animal Research Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, 362-763, Republic of Korea.
authors.forename: Hyeong-Jin
authors.initials: HJ
authors.lastname: Ji
authors.affiliation: Laboratory Animal Research Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, 362-763, Republic of Korea.
authors.forename: Yun-Bae
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea; Research Institute of DiNonA Inc., Seoul, 138-736, Republic of Korea; Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea. Electronic address: hgsong@chungbuk.ac.kr.
authors.forename: Hyung Geun
authors.initials: HG
authors.lastname: Song
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000595:Amino Acid Sequence; D000818:Animals; D023102:Anoikis / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology*; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D000939:Epitopes; D058851:GPI-Linked Proteins; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D017239:Paclitaxel
keywords: Anoikis; CEACAM6; Lung adenocarcinoma; Paclitaxel; Therapeutic antibody