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.
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Authors | Tomonori Tawara, Kazumasa Hasegawa, Yusuke Sugiura, Tomoyuki Tahara, Isao Ishida, Shiro Kataoka |
Journal | Cancer science
(Cancer Sci)
Vol. 98
Issue 6
Pg. 921-8
(Jun 2007)
ISSN: 1347-9032 [Print] England |
PMID | 17428256
(Publication Type: Journal Article)
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Chemical References |
- Antibodies, Monoclonal
- Escherichia coli Proteins
- HLA-DR Antigens
- Adenosine Triphosphatases
- Hda protein, E coli
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Topics |
- Adenosine Triphosphatases
- Animals
- Antibodies, Monoclonal
(pharmacology, therapeutic use)
- B-Lymphocytes
(immunology)
- Cell Line
- Cytotoxicity, Immunologic
- Epitope Mapping
- Escherichia coli Proteins
- HLA-DR Antigens
(immunology)
- Humans
- Lymphoma
(genetics, therapy)
- Mice
- Mice, Transgenic
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