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Original Article

Chimeric anti-podoplanin antibody suppresses tumor metastasis through neutralization and antibody-dependent cellular cytotoxicity

  1. Mika Kato Kaneko1,†,
  2. Akiko Kunita2,†,
  3. Shinji Abe3,†,
  4. Yuta Tsujimoto1,4,†,
  5. Masashi Fukayama2,
  6. Kaoru Goto4,
  7. Yoshihiko Sawa5,
  8. Yasuhiko Nishioka6,
  9. Yukinari Kato1,*

Article first published online: 26 AUG 2012

DOI: 10.1111/j.1349-7006.2012.02385.x

Issue

Cancer Science

Cancer Science

Volume 103, Issue 11, pages 1913–1919, November 2012

Additional Information

How to Cite

(Cancer Sci 2012; 103: 1913–1919)

Author Information

  1. 1

    Molecular Tumor Marker Research Team, Global COE Program, Yamagata University Faculty of Medicine, Yamagata, Japan

  2. 2

    Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

  3. 3

    Practice Room for Clinical Pharmacy, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

  4. 4

    Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata, Japan

  5. 5

    Department of Morphological Biology, Fukuoka Dental College, Fukuoka, Japan

  6. 6

    Department of Respiratory Medicine and Rheumatology, The University of Tokushima Graduate School, Tokushima, Japan

  1. †

    These authors contributed equally to this work.

* To whom correspondence should be addressed.
E-mail: yukinari-k@bea.hi-ho.ne.jp

  1. †

    These authors contributed equally to this work.

Publication History

  1. Issue published online: 29 OCT 2012
  2. Article first published online: 26 AUG 2012
  3. Accepted manuscript online: 20 JUL 2012 11:29AM EST
  4. Manuscript Accepted: 16 JUL 2012
  5. Manuscript Revised: 9 JUL 2012
  6. Manuscript Received: 23 APR 2012

Funded by

  • KAKENHI. Grant Numbers: 22390345, 23659884, 18590855, 23790185, 23701043, 23791584
  • Ministry of Education, Culture, Sports, Science and Technology of Japan
  • SENSHIN Medical Research Foundation
  • Children's Cancer Association of Japan
  • Intelligent Cosmos Academic Foundation
  • Office for Gender Equality of Yamagata University

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Podoplanin is a platelet aggregation-inducing factor associated with tumor metastasis, malignant progression, and cancer stem cells. We produced a rat–human chimeric anti-podoplanin mAb, NZ-8, from rat anti-podoplanin mAb (NZ-1). Although both NZ-1 and NZ-8 possess high binding affinities and high neutralizing activities of platelet aggregation, the antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity of NZ-8 were much higher than NZ-1. Furthermore, both NZ-1 and NZ-8 inhibited the growth of podoplanin-expressing tumors in vivo. Both NZ-1 and NZ-8 also suppressed hematogenous metastasis of podoplanin-expressing tumors. These results suggest that anti-podoplanin mAbs suppressed hematogenous metastasis by both neutralization and antibody-dependent cellular cytotoxicity/complement-dependent cytotoxicity activities. Targeting therapy to podoplanin-expressing tumors should be useful as a novel immunotherapy.

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