Tawara Tomonori, Hasegawa Kazumasa, Sugiura Yusuke, Tahara Tomoyuki, Ishida Isao, Kataoka Shiro
Pharmaceutical Research Laboratories, Kirin Brewing Company, Ltd, Gunma, Japan.
Cancer Sci. 2007 Jun;98(6):921-8. doi: 10.1111/j.1349-7006.2007.00469.x. Epub 2007 Apr 12.
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.
HD8是一种针对人类白细胞抗原-DR（HLA-DR）的全人源单克隆抗体，它是通过使用携带人类免疫球蛋白基因的转染色体小鼠产生的。HD8能够与所有13种测试的HLA-DR阳性细胞系以及来自健康供体的35个B细胞结合。表位作图显示，虽然该抗体识别HLA-DRB链的最具多态性的区域，但其关键表位残基在主要等位基因中是保守的。实际上，HD8能够识别99.2%的HLA-DRB等位基因。由于其必需的表位残基在HLA-DP和HLA-DQ中也大多保守，HD8能够分别识别100%和66%的测试HLA-DP和HLA-DQ等位基因。HD8在体外发挥了强烈的抗体依赖性细胞毒性和补体依赖性细胞毒性，并显著延长了接种非霍奇金淋巴瘤细胞系的免疫受损小鼠的寿命。HD8抗体在针对HLA-DR的免疫治疗中可能非常有用，因为它可能在携带不同HLA-DR等位基因的个体中引发类似的强烈反应。
