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

亲本鼠单克隆抗体 MX35 (Anti-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

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

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.

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