Format

Send to

Choose Destination
Biomaterials. 2015 Oct;67:32-41. doi: 10.1016/j.biomaterials.2015.07.012. Epub 2015 Jul 14.

Therapeutic effect of anti CEACAM6 monoclonal antibody against lung adenocarcinoma by enhancing anoikis sensitivity.

Author information

1
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.
2
Research Institute of DiNonA Inc., Seoul, 138-736, Republic of Korea.
3
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.
4
Department of Pathology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
5
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.
6
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.
7
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.
8
Research Institute, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
9
Laboratory Animal Research Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, 362-763, Republic of Korea.
10
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.

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.

KEYWORDS:

Anoikis; CEACAM6; Lung adenocarcinoma; Paclitaxel; Therapeutic antibody

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center