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Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy

  • Authors:
    • Anja C. Mortensen
    • Diana Spiegelberg
    • Anna-Karin Haylock
    • Hans Lundqvist
    • Marika Nestor
  • View Affiliations / Copyright

    Affiliations: Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185 Uppsala, Sweden, Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden
    Copyright: © Mortensen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1875-1885
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    Published online on: April 11, 2018
       https://doi.org/10.3892/ijo.2018.4364
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Abstract

CD44v6 is overexpressed in a variety of cancers, rendering it a promising target for radio-immunotherapy (RIT). In this study, we have characterized a novel engineered recombinant monoclonal anti-CD44v6 antibody, AbN44v6, and assessed its potential for use in RIT using either 177Lu or 131I as therapeutic radionuclides. In vitro affinity and specificity assays characterized the binding of the antibody labeled with 177Lu, 125I or 131I. The therapeutic effects of 177Lu-AbN44v6 and 131I-AbN44v6 were investigated using two in vitro 3D tumor models with different CD44v6 expression. Finally, the normal tissue biodistribution and dosimetry for 177Lu-AbN44v6 and 125I-AbN44v6/131I-AbN44v6 were assessed in vivo using a mouse model. All AbN44v6 radioconjugates demonstrated CD44v6-specific binding in vitro. In the in vitro 3D tumor models, dose-dependent therapeutic effects were observed with both 177Lu-AbN44v6 and 131I-AbN44v6, with a greater significant therapeutic effect observed on the cells with a higher CD44v6 expression. Biodistribution experiments demonstrated a greater uptake of 177Lu-AbN44v6 in the liver, spleen and bone, compared to 125I-AbN44v6, whereas 125I-AbN44v6 demonstrated a longer circulation time. In dosimetric calculations, the critical organs for 177Lu-AbN44v6 were the liver and spleen, whereas the kidneys and red marrow were considered the critical organs for 131I-AbN44v6. The effective dose was in the order of 0.1 mSv/MBq for both labels. In conclusion, AbN44v6 bound specifically and with high affinity to CD44v6. Furthermore, in vitro RIT demonstrated growth inhibition in a CD44v6-specific activity-dependent manner for both radioconjugates, demonstrating that both 177Lu-AbN44v6 and 131I-AbN44v6 may be promising RIT candidates. Furthermore, biodistribution and dosimetric analysis supported the applicability of both conjugates for RIT. The CD44v6-specific therapeutic effects observed with radiolabeled AbN44v6 in the 3D tumor models in vitro, combined with the beneficial dosimetry in vivo, render AbN44v6 a potential candidate for RIT.
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Copy and paste a formatted citation
Spandidos Publications style
Mortensen AC, Spiegelberg D, Haylock A, Lundqvist H and Nestor M: Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy. Int J Oncol 52: 1875-1885, 2018.
APA
Mortensen, A.C., Spiegelberg, D., Haylock, A., Lundqvist, H., & Nestor, M. (2018). Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy. International Journal of Oncology, 52, 1875-1885. https://doi.org/10.3892/ijo.2018.4364
MLA
Mortensen, A. C., Spiegelberg, D., Haylock, A., Lundqvist, H., Nestor, M."Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy". International Journal of Oncology 52.6 (2018): 1875-1885.
Chicago
Mortensen, A. C., Spiegelberg, D., Haylock, A., Lundqvist, H., Nestor, M."Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy". International Journal of Oncology 52, no. 6 (2018): 1875-1885. https://doi.org/10.3892/ijo.2018.4364
Copy and paste a formatted citation
x
Spandidos Publications style
Mortensen AC, Spiegelberg D, Haylock A, Lundqvist H and Nestor M: Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy. Int J Oncol 52: 1875-1885, 2018.
APA
Mortensen, A.C., Spiegelberg, D., Haylock, A., Lundqvist, H., & Nestor, M. (2018). Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy. International Journal of Oncology, 52, 1875-1885. https://doi.org/10.3892/ijo.2018.4364
MLA
Mortensen, A. C., Spiegelberg, D., Haylock, A., Lundqvist, H., Nestor, M."Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy". International Journal of Oncology 52.6 (2018): 1875-1885.
Chicago
Mortensen, A. C., Spiegelberg, D., Haylock, A., Lundqvist, H., Nestor, M."Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy". International Journal of Oncology 52, no. 6 (2018): 1875-1885. https://doi.org/10.3892/ijo.2018.4364
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