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首页> 外文期刊>Antibodies >Immunotherapy of B-Cell Lymphoma with an Engineered Bispecific Antibody Targeting CD19 and CD5
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Immunotherapy of B-Cell Lymphoma with an Engineered Bispecific Antibody Targeting CD19 and CD5

机译：用靶向CD19和CD5的工程化双特异性抗体对B细胞淋巴瘤进行免疫治疗

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摘要

Using genetic engineering a humanized Fab fragment with specificity for CD19 was fused to a disulfide-stabilized single-chain antibody (dsFv) recognizing CD5. This format should show reduced immunogenicity and improved tissue penetration. The specificity of bsAb FabCD19xdsFvCD5 binding to target cells was verified by flow cytometry on B and T lymphoma cell lines. Binding affinities of both arms were compared with the bivalent parental antibodies against CD19 and CD5 by binding competition assay. Redirected lysis of B lymphoma cells by preactivated PBMC from healthy donors was demonstrated in a chromium-release assay. A clear dose-response relationship could be established in the range from 1 ng/mL to 10 μg/mL bsAb. To evaluate the in vivo efficacy of bsAb FabCD19xdsFvCD5, NOD/SCID mice were intravenously injected with luciferase transfected Raji lymphoma cells together with pre-activated PBMC. Mice received five injections of therapeutic bsAb or control antibodies. While in the control groups all mice died within 40 to 50 days, 40% of bsAb treated animals survived longer than 60 days.
机译：使用基因工程，将对CD19具有特异性的人源化Fab片段与识别CD5的二硫键稳定的单链抗体（dsFv）融合。这种形式应显示出降低的免疫原性和改善的组织渗透性。 bsAb FabCD19xdsFvCD5与靶细胞结合的特异性通过在B和T淋巴瘤细胞系上的流式细胞术验证。通过结合竞争测定法将两个臂的结合亲和力与针对CD19和CD5的二价亲本抗体进行比较。在铬释放试验中证实了来自健康供体的预活化PBMC对B淋巴瘤细胞的重定向裂解。可以在1 ng / mL至10μg/ mL bsAb范围内建立明确的剂量反应关系。为了评估bsAb FabCD19xdsFvCD5的体内功效，向NOD / SCID小鼠静脉内注射荧光素酶转染的Raji淋巴瘤细胞以及预激活的PBMC。小鼠接受了五次治疗性bsAb或对照抗体的注射。在对照组中，所有小鼠均在40至50天内死亡，而40％bsAb治疗的动物存活时间超过60天。

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