Researchers at UCLA's Jonsson Cancer Center have uncovered themechanism by which an antibody blocks the growth of prostate cancer inanimal models, a discovery that could pave the way for development of anew molecularly targeted therapy.
The antibody, called 1G8 and discovered by UCLA scientists, signalsthe prostate cancer cells to stop growing and die, said Dr. Robert E.Reiter, a Jonsson Cancer Center researcher and professor of urology.The antibody proved effective in several different animal models ofprostate cancer, Reiter said, indicating that is could be a potentcancer fighter.
The research appears in the Oct. 15 issue of Cancer Research, apeer-reviewed journal published by the American Association for CancerResearch.
The 1G8 antibody binds to prostate stem cell antigen or PSCA, acell surface protein discovered by Reiter that is found in about 95percent of early stage prostate cancers and about 87 percent ofprostate cancers that have spread to the bones. PSCA also is found inbladder and pancreatic cancers, Reiter and his team previouslydiscovered, so a new targeted therapy developed from the antibody mayalso prove effective in battling those cancers.
"The big question with antibodies has been, how do they work?"said Reiter, senior author of the study. "Do antibodies recruit theimmune system to kill the cancer or do they send a signal that tellsthe cancer cells to stop growing? This study shows how the antibodyworks, so we'll know how to apply it in the clinical setting."
The 1G8 antibody has two parts, one that binds with PSCA andone that binds with macrophages, the immune system's killer cells.Reiter and his team fragmented the antibody, separating the part thatbinds to PSCA and testing it alone in the animal models to see how itaffected the prostate cancer cells. Even without engaging an immuneresponse, the antibody blocked the growth of the prostate cancer cells.
"The fragments we created were unable to bind to the immunesystem, but they retained the same activity the whole antibody showed,so we proved that 1G8 must work by signaling the cancer cells to stopgrowing and die," Reiter said. "That's important because it provides alot more information about what PSCA does and how antibodies work. Italso suggests that PSCA is a very good target for therapy and that ourantibody, in particular, is extremely active and binds to a region onthe cell surface protein that may be an optimal target for a newtreatment."
Molecularly targeted therapies are the new wave of cancertherapy, homing in on what is broken or mutated in the cancer cells andleaving the healthy cells alone. Because they only target the cancercells, these therapies typically cause few side effects, if any, andare much easier for patients to tolerate.
The next step, Reiter said, is to test the 1G8 antibody in human clinical trials, probably in about a year.
This study is the result of years of laboratory research and ispart of the Jonsson Cancer Center's Specialized Program of ResearchExcellence in prostate cancer, a National Cancer Institute-fundedprogram to discover new and better ways to prevent, detect and treatprostate cancer.
"This work from start to finish is a UCLA discovery, truetranslational research that will go from the lab bench to the patientbedside," Reiter said.
Prostate cancer will strike more than 232,000 men in theUnited States this year alone, killing more than 30,350. Prostatecancer is the second leading cause of cancer death in men, according tothe American Cancer Society.
UCLA's Jonsson Comprehensive Cancer Center comprises more than 240researchers and clinicians engaged in cancer research, prevention,detection, control, treatment and education. One of the nation'slargest comprehensive cancer centers, the Jonsson Cancer Center isdedicated to promoting research and translating the results intoleading-edge clinical studies. In July 2005, the Jonsson Cancer Centerwas named the best cancer center in the western United States by U.S.News & World Report, a ranking it has held for six consecutiveyears.
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