A Radiolabeled Fully Human Antibody to Human Aspartyl (Asparaginyl) β-Hydroxylase Is a Promising Agent for Imaging and Therapy of Metastatic Breast Cancer

Ekaterina Revskaya, Zewei Jiang, Alfred Morgenstern, Frank Bruchertseifer, Muctarr Sesay, Susan Walker, Steven Fuller, Michael S. Lebowitz, Claudia Gravekamp, Hossein A. Ghanbari, Ekaterina Dadachova

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

There is a need for novel effective and safe therapies for metastatic breast cancer based on targeting tumor-specific molecular markers of cancer. Human aspartyl (asparaginyl) β-hydroxylase (HAAH) is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins and is overexpressed in a variety of cancers, including breast cancer. A fully human monoclonal antibody (mAb) PAN-622 has been developed to HAAH. In this study, they describe the development of PAN-622 mAb as an agent for imaging and radioimmunotherapy of metastatic breast cancer. PAN-622 was conjugated to several ligands such as DOTA, CHXA″, and DTPA to enable subsequent radiolabeling and its immunoreactivity was evaluated by an HAAH-specific enzyme-linked immunosorbent assay and binding to the HAAH-positive cells. As a result, DTPA-PAN-622 was chosen to investigate biodistribution in healthy CD-1 female mice and 4T1 mammary tumor-bearing BALB/c mice. The 111In-DTPA-pan622 mAb concentrated in the primary tumors and to some degree in lung metastases as shown by SPECT/CT and Cherenkov imaging. A pilot therapy study with 213Bi - DTPA-PAN-622 demonstrated a significant effect on the primary tumor. The authors concluded that human mAb PAN-622 to HAAH is a promising reagent for development of imaging and possible therapeutic agents for the treatment of metastatic breast cancer.

Original languageEnglish (US)
Pages (from-to)57-65
Number of pages9
JournalCancer Biotherapy and Radiopharmaceuticals
Volume32
Issue number2
DOIs
StatePublished - Mar 1 2017

Keywords

  • In, Bi, HAAH, metastatic breast cancer, PAN-622 human antibody, radioimmunotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

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    Revskaya, E., Jiang, Z., Morgenstern, A., Bruchertseifer, F., Sesay, M., Walker, S., Fuller, S., Lebowitz, M. S., Gravekamp, C., Ghanbari, H. A., & Dadachova, E. (2017). A Radiolabeled Fully Human Antibody to Human Aspartyl (Asparaginyl) β-Hydroxylase Is a Promising Agent for Imaging and Therapy of Metastatic Breast Cancer. Cancer Biotherapy and Radiopharmaceuticals, 32(2), 57-65. https://doi.org/10.1089/cbr.2016.2141