The Scripps Research Institute
Study authors Xiuling Li (left) and Christoph Rader Photo courtesy of Junpeng Qi and
A class of antibody-drug conjugates (ADCs) have shown promise for treating hematologic and solid tumor malignancies, according to research published in Cell Chemical Biology.
The ADCs, known as selenomab-drug conjugates, demonstrated in vitro activity against breast cancer and multiple myeloma (MM).
The ADCs also inhibited tumor growth and prolonged survival in mouse models of both malignancies.
“We’ve been working on this technology for some time,” said study author Christoph Rader, PhD, of The Scripps Research Institute (TSRI) in Jupiter, Florida.
“It’s based on the rarely used natural amino acid selenocysteine, which we insert into our antibodies. We refer to these engineered antibodies as selenomabs.”
He then explained that selenomab-drug conjugates are ADCs that “utilize the unique reactivity of selenocysteine for drug attachment.”
For this study, Dr Rader and his colleagues generated selective selenomab-drug conjugates and tested them in vitro and in vivo.
The team found that CD138-targeting selenomab-drug conjugates were effective against MM cell lines (U266 and H929), and HER2-targeting selenomab-drug conjugates were effective against breast cancer cell lines.
Both types of ADCs demonstrated efficacy in mouse models as well.
One of the CD138-targeting selenomab-drug conjugates, known as CN29, was tested in a mouse model of MM.
One group of mice received CN29 at 3 mg/kg every 4 days for a total of 4 cycles, another group received unconjugated selenomab, and a third received vehicle control.
CN29 significantly inhibited tumor growth (P=0.000085) and extended survival time (P=0.0083) in the mice.
Based on these results, Dr Rader said selenomab-drug conjugates “promise broad utility for cancer therapy.”
