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) b-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 HAAHspecific 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.

REVSKAYA Ekaterina;  JIANG Z.;  MORGENSTERN Alfred;  BRUCHERTSEIFER Frank;  SESAY M;  WALKER S;  FULLER S;  LEBOWITZ Ms;  GRAVEKAMP C;  GHANBARI Ha;  DADACHOVA E.; 

2017-03-22

MARY ANN LIEBERT

JRC101456

1084-9785,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC101456,   

10.1089/cbr.2016.2141,