In mice carrying specimens of human breast cancer, treatment with a genetically engineered mini-antibody, or “diabody,” laden with a radioactive isotope significantly impeded the growth of the tumors, researchers report.

“Overall, we are very pleased with the results, which show that anti-tumor diabody-based radioimmunotherapy can be an effective form of therapy,” Dr. Gregory P. Adams from the Fox Chase Cancer Center in Philadelphia told Reuters Health.

Since the mid-1980s, so-called monoclonal antibodies have become familiar as a way to target isotopes to tumor cells. “This approach is hindered by the large size of monoclonal antibodies and their very nature, which is to remain in the blood a long time,” Dr. Adams explained.

Diabodies, which are one-third the size of monoclonal antibodies, are better able to penetrate tumors and are cleared rapidly from the bloodstream.

In mice, a single dose of diabodies tagged with yttrium-90 significantly delayed the rate of growth of implanted human breast tumors, but fell short of inhibiting human ovarian cancers, Adams’ team reports in the journal Cancer Research.

The differing response of the two types of tumor is not all that surprising, Adams said, and could be due to a number of factors including a higher rate of diabody uptake in mammary versus ovarian tumors.

Adams admitted he’s “a little bit concerned” kidney damage. Some mice examined 1 year after diabody therapy displayed varying degrees of impaired kidney function.

Rather than using yttrium-90, “we may actually head toward iodine-131 as the therapeutic agent because that will not stay in the kidney,” he said.

His team has now completed additional studies using alpha-emitting radioisotopes (yttrium-90 is a beta emitter) and the results are even more promising. “In a study we’ve repeated twice now, 1 year after therapy, we’ve gotten about three complete responders out of five treated mice - with no toxicity.”

SOURCE: Cancer Research, September 1, 2004.