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Fully human antibody exhibits pan-human leukocyte antigen-DR recognition and high in vitro/vivo efficacy against human leukocyte antigen-DR-positive lymphomas

  1. Tomonori Tawara1,3,
  2. Kazumasa Hasegawa1,
  3. Yusuke Sugiura1,
  4. Tomoyuki Tahara1,
  5. Isao Ishida2,
  6. Shiro Kataoka1,3,*

Article first published online: 12 APR 2007

DOI: 10.1111/j.1349-7006.2007.00469.x

Issue

Cancer Science

Cancer Science

Volume 98, Issue 6, pages 921–928, June 2007

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How to Cite

Tawara, T., Hasegawa, K., Sugiura, Y., Tahara, T., Ishida, I. and Kataoka, S. (2007), Fully human antibody exhibits pan-human leukocyte antigen-DR recognition and high in vitro/vivo efficacy against human leukocyte antigen-DR-positive lymphomas. Cancer Science, 98: 921–928. doi: 10.1111/j.1349-7006.2007.00469.x

Author Information

  1. 1

    Pharmaceutical Research Laboratories and

  2. 2

    Pharmaceutical Frontier Laboratory, Kirin Brewery Company, Ltd, Gunma 370-1295;

  3. 3

    Department of Biological and Chemical Engineering, Faculty of Engineering, Gunma University, Gunma 376-8515, Japan

* To whom correspondence should be addressed. E-mail: s-kataoka@kirin.co.jp

Publication History

  1. Issue published online: 12 APR 2007
  2. Article first published online: 12 APR 2007
  3. (Received December 24, 2006/Revised February 14, 2007/Accepted February 21, 2007/Online publication April 6, 2007)

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HD8, a fully human monoclonal antibody specific for human leukocyte antigen-DR (HLA-DR), was generated by using the transchromosome mouse that bears the human immunoglobulin genes. HD8 could bind to all 13 tested HLA-DR-positive cell lines and 35 B-cells from healthy donors. Epitope mapping revealed that while the antibody recognizes the most polymorphic region of the HLA-DRB chain, its critical epitope residues are conserved in the major alleles. Indeed, HD8 could recognize 99.2% of HLA-DRB alleles. Since its essential epitope residues are also largely conserved in HLA-DP and HLA-DQ, HD8 could recognize 100% and 66% of the HLA-DP and HLA-DQ alleles tested, respectively. HD8 exerted strong antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro, and significantly extended the life span of immunocompromised mice inoculated with non-Hodgkin lymphoma cell lines. The HD8 antibody may be highly useful in HLA-DR-targeted immunotherapy as it is likely to evoke similarly strong responses in individuals carrying different HLA-DR alleles. (Cancer Sci 2007; 98: 921–928)

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