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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibody Affinity
  • Antibody Specificity
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / pharmacology
  • Astatine / chemistry
  • Carcinoma / diagnostic imaging*
  • Carcinoma / genetics
  • Carcinoma / immunology
  • Carcinoma / therapy
  • Cell Line, Tumor
  • Female
  • Gene Expression
  • Humans
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / diagnostic imaging*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / therapy
  • Radioimmunotherapy
  • Radiopharmaceuticals / chemistry
  • Sodium-Phosphate Cotransporter Proteins, Type IIb / genetics
  • Sodium-Phosphate Cotransporter Proteins, Type IIb / metabolism
  • Technetium / chemistry
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Radiopharmaceuticals
  • SLC34A2 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type IIb
  • Technetium
  • Astatine

Grants and funding

This work was supported by the King Gustaf V Jubilee Clinic Cancer Research Foundation in Gothenburg, Sweden and the Swedish Cancer Society (2013-642 and 644), and by CNPq and FINEP, in Brasil. Recepta Biopharma provided support in the form of salaries for authors Luciana N. S. Andrade, Bruno Brasil Horta, Oswaldo Keith Okamoto and Maria Carolina B. Tuma, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.