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亲本鼠单克隆抗体MX35（抗NaPi2b）及其人源化版本Rebmab200的结合亲和力、特异性和比较生物分布

Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200.

作者信息

Lindegren Sture, Andrade Luciana N S, Bäck Tom, Machado Camila Maria L, Horta Bruno Brasil, Buchpiguel Carlos, Moro Ana Maria, Okamoto Oswaldo Keith, Jacobsson Lars, Cederkrantz Elin, Washiyama Kohshin, Aneheim Emma, Palm Stig, Jensen Holger, Tuma Maria Carolina B, Chammas Roger, Hultborn Ragnar, Albertsson Per

机构信息

Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg,Gothenburg, Sweden.

Recepta Biopharma, São Paulo, Brasil; Centro de Investigação Translacional em Oncologia (LIM24), Instituto do Câncer do Estado de São Paulo, Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.

出版信息

PLoS One. 2015 May 13;10(5):e0126298. doi: 10.1371/journal.pone.0126298. eCollection 2015.

DOI:10.1371/journal.pone.0126298
PMID:25970341
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4430291/
Abstract

The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with 211At-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated, as was the utility of 99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that 99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.

摘要

这项临床前研究的目的是评估单克隆抗体Rebmab200的特性，它是卵巢特异性鼠源抗体MX35的人源化版本。本研究为未来使用211At-Rebmab200对微小残留卵巢癌进行临床α放射免疫治疗奠定了基础。在此，评估了211At-Rebmab200的生物分布以及99mTc-Rebmab200用于生物成像的效用。在结合固定化NaPi2B表位和活细胞的体外能力方面，将Rebmab200与其鼠源对应物MX35进行了直接比较；我们还评估了其在携带皮下OVCAR-3肿瘤的裸鼠中的生物分布。Rebmab200和鼠源MX35之间的肿瘤抗原和细胞结合情况相似，生物分布情况也相似，包括正常组织摄取和体内肿瘤结合。我们还证明，99mTc-Rebmab200可用于荷瘤小鼠皮下卵巢癌的单光子发射计算机断层扫描。综上所述，我们的数据支持进一步开发Rebmab200用于放射免疫治疗和诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/bfd70e75fa5f/pone.0126298.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/87f30964d025/pone.0126298.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/4fe172bf3a70/pone.0126298.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/48867165231e/pone.0126298.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/1cf05e4f3308/pone.0126298.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/bfd70e75fa5f/pone.0126298.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/87f30964d025/pone.0126298.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/4fe172bf3a70/pone.0126298.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/48867165231e/pone.0126298.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/1cf05e4f3308/pone.0126298.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6996/4430291/bfd70e75fa5f/pone.0126298.g005.jpg

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