Researchers from City of Hope and the University of California, Los Angeles (UCLA), have developed a molecule that may one day make prostate cancer diagnosis more effective.
Mark Sherman, Ph.D., associate professor in the Department of Cancer Immunotherapeutics and Tumor Immunology, worked with UCLA colleagues to genetically engineer a protein that seeks out and attaches itself to prostate cancer cells.
|Molecular ribbon model of a diabody (Image by Mark Sherman)|
The protein, dubbed a “diabody,” carries a radioactive isotope that makes prostate tumors visible inside the body through the imaging technology known as positron emission tomography, or PET. Physicians need better isotope-carrying proteins to see prostate tumors through non-invasive scans, because current carriers work poorly for this form of cancer.
The work, published in the March issue of Protein Engineering Design & Selection, builds on a long-standing collaboration between the two institutions that aims to make an antibody more effective at finding prostate cancer cells.
Researchers previously produced an antibody in mice that attaches to human prostate cancer cells. But when they made the antibody more “human,” it became less likely to stick to prostate cancer cells. The antibody also lingered in the bloodstream too long, clouding the PET images.
To combat these challenges, the researchers further engineered the antibody, trimming it down to just the active pieces and joining them with a short piece of protein called a linker. This new molecule, called a diabody, was better at clearing out of the bloodstream quickly.
Sherman then turned his sights to making the antibody bind better to prostate tumors. By creating three-dimensional virtual models of the diabody, he found key points in the protein that might make the diabody stick to prostate cancer cells better.
Following Sherman’s advice, the UCLA researchers re-engineered the diabody in the laboratory and found that it regained much of its stickiness.
“We also found that adjusting the length of the linker made the diabody more stable,” said Sherman. This is important for making sure the diabody reaches its target and remains there for imaging, he explained.
More study is needed, but researchers hope the work will lead to improved diagnosis of prostate cancer and possibly other cancers, as well.