Fully human antibody exhibits pan-human leukocyte antigen-DR recognition and high in vitro/vivo efficacy against human leukocyte antigen-DR-positive lymphomas
Authors: Tawara, Tomonori; Hasegawa, Kazumasa1; Sugiura, Yusuke1; Tahara, Tomoyuki1; Ishida, Isao2; Kataoka, Shiro
Source: Cancer Science, Volume 98, Number 6, June 2007 , pp. 921-928(8)
Publisher: Blackwell Publishing
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Abstract:
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)Document Type: Research article
DOI: 10.1111/j.1349-7006.2007.00469.x
Affiliations: 1: Pharmaceutical Research Laboratories and 2: Pharmaceutical Frontier Laboratory, Kirin Brewery Company, Ltd, Gunma 370-1295;
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