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

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.

• Authors: Ekaterina Revskaya, Zewei Jiang, Alfred Morgenstern, Frank Bruchertseifer, Muctarr Sesay, Susan Walker, Steven Fuller, Michael S Lebowitz, Claudia Gravekamp, Hossein A Ghanbari, Ekaterina Dadachova
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 32 Issue 2 Pg. 57-65 (Mar 2017) ISSN: 1557-8852 [Electronic] United States
• PMID: 28301261 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Ligands
• Mixed Function Oxygenases
• aspartic acid 2-oxoglutarate-dependent dioxygenase

Topics

• Animals
• Antibodies, Monoclonal (chemistry)
• Breast Neoplasms (diagnostic imaging, drug therapy, radiotherapy)
• Cell Line, Tumor
• Diagnostic Imaging (methods)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Ligands
• Mice
• Mice, Inbred BALB C
• Mixed Function Oxygenases (chemistry)
• Neoplasm Metastasis
• Radioimmunotherapy (methods)
• Tissue Distribution