One drug, two targets

Targeted therapies are the new paradigm in cancer treatment and researchers at Fox Chase Cancer Center in Philadelphia are developing the second generation of these antibody-based drugs. Ongoing research at Fox Chase has demonstrated the ability of recombinantly engineered bispecific monoclonal antibodies to attack two separate targets on a single cancer cell. Most recently, the Fox Chase laboratory of Gregory P. Adams, Ph.D., has done preclinical tests of bispecific molecules carrying a radioactive isotope that can be used to detect or kill a tumor.

"What is unique is that these bispecific antibodies are expected to make the targeted tumor cells more sensitive to the radiation," said Adams, a researcher in the medical science division at Fox Chase Cancer Center. Adams presented his research today at the 94th annual meeting of the American Association for Cancer Research, July 11-14 in Washington, D.C.

Targeted cancer therapies work by attacking a single target on the surface of the cell, either delivering a toxic payload or directly causing it to stop multiplying or die. "Unfortunately, there is a lot of redundancy in cancer cells, making it difficult to kill a tumor with a single hit," Adams pointed out. "We wanted both to refine the tumor specificity of the antibodies and to increase their ability to kill the targeted cells.

"Our targets are members of the epidermal growth factor receptor family, a powerful group of signaling proteins that are found in many commonly occurring cancers. These receptors interact with each other to instruct cells to grow and resist the effects of many cancer cells. Simultaneously targeting pairs of these receptors can increase the specificity of tumor-cell targeting and block their signaling functions, thus making the cells more sensitive to treatment.

"Attaching radioisotopes to this molecule adds insult to injury and gives us a better chance to destroy cancer cells without attacking normal


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