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Preliminary biological evaluation of 123I-labelled anti-CD30-LDM in CD30-positive lymphomas murine models.
Artificial Cells, Nanomedicine, and Biotechnology ( IF 5.8 ) Pub Date : 2020-01-09 , DOI: 10.1080/21691401.2019.1709857
Jianhua Gong 1 , Feihu Guo 2 , Weihua Cheng 2 , Hongqiang Fan 2 , Qingfang Miao 1 , Jigang Yang 3
Affiliation  

Overexpression of CD30 has been reported on the surface of some T-cell lymphomas, especially on Hodgkin's lymphoma (HL) and anaplastic large cell lymphoma (ALCL). CD30 targeted immunotherapy has good clinical therapy response. We have produced a novel antibody drug conjugates (ADCs)-anti-CD30-LDM, which shows attractive tumour-targeting capability and extremely potent antitumor efficacy. To further investigate biological characteristics and promote clinical translation of anti-CD30-LDM, we constructed a radiolabeled 123I-anti-CD30-LDM to evaluate the biodistribution characteristics. The anti-CD30-LDM was radioiodinated by the Iodogen method. The radiochemical purity of 123I-anti-CD30-LDM was more over 98%, and the specific activity of 240.5 MBq/mg. The stability and the specificity of 123I-anti-CD30-LDM were evaluated in vitro. Cellular binding assays were used to evaluate the binding capabilities in CD30-positive Karpas299 cells and CD30-negative Raji cells. B-NDG mice bearing Karpas 299 and Raji xenografts were used for in vivo biodistribution studies. Our results demonstrated that anti-CD30-LDM as an ideal ADC targeted to CD30, which was labelled easily with 123I and obtained the sufficient yields. The 123I-anti-CD30-LDM preserved specific binding to CD30 in vitro and uptake in tumour xenografts in B-NDG mice. These results are encouraging for anti-CD30-LDM as a promising clinical translational candidate for various CD30 positive lymphomas and other diseases.

中文翻译:

CD30阳性淋巴瘤小鼠模型中123I标记的抗CD30-LDM的初步生物学评估。

据报道,CD30在某些T细胞淋巴瘤的表面过度表达,特别是在霍奇金淋巴瘤(HL)和间变性大细胞淋巴瘤(ALCL)上。CD30靶向免疫治疗具有良好的临床治疗反应。我们已经生产了一种新型的抗体药物偶联物(ADCs)-抗CD30-LDM,它具有有吸引力的肿瘤靶向能力和极强的抗肿瘤功效。为了进一步研究生物学特性并促进抗CD30-LDM的临床翻译,我们构建了放射性标记的123I-抗CD30-LDM来评估生物分布特性。抗CD30-LDM通过碘法进行放射性碘标记。123I-抗CD30-LDM的放射化学纯度超过98%,比活度为240.5 MBq / mg。在体外评估了123I-抗CD30-LDM的稳定性和特异性。细胞结合测定法用于评估在CD30阳性Karpas299细胞和CD30阴性Raji细胞中的结合能力。携带Karpas 299和Raji异种移植物的B-NDG小鼠用于体内生物分布研究。我们的结果表明,抗CD30-LDM是靶向CD30的理想ADC,可轻松用123I标记,并获得足够的产率。123I-抗CD30-LDM在体外保留了与CD30的特异性结合,并在B-NDG小鼠的异种移植物中被摄取。这些结果对于抗CD30-LDM作为各种CD30阳性淋巴瘤和其他疾病的有希望的临床转化候选者而言是令人鼓舞的。携带Karpas 299和Raji异种移植物的B-NDG小鼠用于体内生物分布研究。我们的结果表明,抗CD30-LDM是靶向CD30的理想ADC,可轻松用123I标记,并获得足够的产率。123I-抗CD30-LDM在体外保留了与CD30的特异性结合,并在B-NDG小鼠的异种移植物中被摄取。这些结果对于抗CD30-LDM作为各种CD30阳性淋巴瘤和其他疾病的有希望的临床转化候选者而言是令人鼓舞的。携带Karpas 299和Raji异种移植物的B-NDG小鼠用于体内生物分布研究。我们的结果表明,抗CD30-LDM作为靶向CD30的理想ADC,可以轻松地用123I标记,并获得足够的产率。123I-抗CD30-LDM在体外保留了与CD30的特异性结合,并在B-NDG小鼠的异种移植物中被摄取。这些结果对于抗CD30-LDM作为各种CD30阳性淋巴瘤和其他疾病的有希望的临床转化候选者而言是令人鼓舞的。
更新日期:2020-12-01
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