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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >T cell costimulus-independent and very efficacious inhibition of tumor growth in mice bearing subcutaneous or leukemic human B cell lymphoma xenografts by a CD19-/CD3- bispecific single-chain antibody construct.
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T cell costimulus-independent and very efficacious inhibition of tumor growth in mice bearing subcutaneous or leukemic human B cell lymphoma xenografts by a CD19-/CD3- bispecific single-chain antibody construct.

机译：CD19- / CD3-双特异性单链抗体构建体在携带皮下或白血病人B细胞淋巴瘤异种移植物的小鼠中不依赖T细胞共刺激并且非常有效地抑制了肿瘤的生长。

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摘要

We have recently demonstrated that a recombinant single-chain bispecific Ab construct, bscCD19xCD3, in vitro induces rapid B lymphoma-directed cytotoxicity at picomolar concentrations with unstimulated peripheral T cells. In this study, we show that treatment of nonobese diabetic SCID mice with submicrogram doses of bscCD19xCD3 could prevent growth of s.c. human B lymphoma xenografts and essentially cured animals when given at an early tumor stage. The effect was dose dependent, dependent on E:T ratio and the time between tumor inoculation and administration of bscCD19xCD3. No therapeutic effect was seen in the presence of human lymphocytes alone, a vehicle control, or with a bispecific single-chain construct of identical T cell-binding activity but different target specificity. In a leukemic nonobese diabetic SCID mouse model, treatment with bscCD19xCD3 prolonged survival of mice in a dose-dependent fashion. The human lymphocytes used as effector cells in both animal models did not express detectable T cell activation markers at the time of coinoculation with tumor cells. The bispecific Ab therefore showed an in vivo activity comparable to that observed in cell culture with respect to high potency and T cell costimulus independence. These properties make bscCD19xCD3 superior to previously investigated CD19 bispecific Ab-based therapies.
机译：我们最近证明重组的单链双特异性抗体构建体bscCD19xCD3，在体外以不受刺激的外周T细胞在皮摩尔浓度下诱导快速B淋巴瘤定向的细胞毒性。在这项研究中，我们表明，用亚微克剂量的bscCD19xCD3治疗非肥胖型糖尿病SCID小鼠可以预防s.c.的生长。在肿瘤早期给予的人B淋巴瘤异种移植物和基本上治愈的动物。该作用是剂量依赖性的，取决于E∶T比和肿瘤接种与bscCD19xCD3给药之间的时间。在单独存在人类淋巴细胞，媒介物对照或具有相同T细胞结合活性但靶特异性不同的双特异性单链构建体的情况下，未观察到治疗效果。在白血病非肥胖型糖尿病SCID小鼠模型中，bscCD19xCD3的治疗以剂量依赖性方式延长了小鼠的存活期。在两种动物模型中用作效应细胞的人淋巴细胞在与肿瘤细胞共接种时均未表达可检测的T细胞活化标记。因此，就高效力和T细胞共刺激独立性而言，双特异性Ab显示出与细胞培养中观察到的相当的体内活性。这些特性使bscCD19xCD3优于先前研究的基于CD19双特异性Ab的疗法。

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