Fully human antibody exhibits pan-human leukocyte antigen-DR recognition and high in vitro/vivo efficacy against human leukocyte antigen-DR-positive lymphomas.
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.
Tawara
Tomonori
T
Pharmaceutical Research Laboratories, Kirin Brewing Company, Ltd, Gunma, Japan.
Hasegawa
Kazumasa
K
Sugiura
Yusuke
Y
Tahara
Tomoyuki
T
Ishida
Isao
I
Kataoka
Shiro
S
D000251:Adenosine Triphosphatases; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D029968:Escherichia coli Proteins; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic
D000911:Antibodies, Monoclonal; D029968:Escherichia coli Proteins; D006684:HLA-DR Antigens; D000251:Adenosine Triphosphatases; C435211:Hda protein, E coli