Preliminary biological evaluation of 123I-labelled anti-CD30-LDM in CD30-positive lymphomas murine models

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-L...

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Published in:Artificial cells, nanomedicine, and biotechnology nanomedicine, and biotechnology, 2020-01, Vol.48 (1), p.408-414
Main Authors: Gong, Jianhua, Guo, Feihu, Cheng, Weihua, Fan, Hongqiang, Miao, Qingfang, Yang, Jigang
Format: Article
Language:English
Subjects:
Anaplastic large-cell lymphoma
Animal models
Antibodies
antibody-drug conjugate
Anticancer properties
Antitumor activity
Binding
biodistribution
CD30
CD30 antigen
Immunotherapy
In vivo methods and tests
Lymphocytes T
Lymphoma
Radiochemistry
Radioimmunoconjugates
Stability analysis
Tumors
Xenografts
Xenotransplantation
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Summary: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 123 I-anti-CD30-LDM to evaluate the biodistribution characteristics. The anti-CD30-LDM was radioiodinated by the Iodogen method. The radiochemical purity of 123 I-anti-CD30-LDM was more over 98%, and the specific activity of 240.5 MBq/mg. The stability and the specificity of 123 I-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 123 I and obtained the sufficient yields. The 123 I-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.
ISSN:2169-1401
2169-141X
DOI:10.1080/21691401.2019.1709857