Antibody developed at Johns Hopkins slows growth of lung, breast cancer tumors

Johns Hopkins scientists have developed an antibody that suppresses the cell growth of lung tumors and breast cancer metastasis in experiments in mice, according to a new study published in the February issue of Nature Communications.

The antibody, dubbed Y4, targets a potassium channel called KCNK9, which is most commonly found in brain tissue and can be overabundant in lung, breast, and other tumor cells. KCNK9's exact role in cancer is unclear, but scientists believe it helps tumor cells survive, grow, and invade normal tissue by behaving like a gateway to control the flow of essential chemical ions.

"Our experiments do not predict how well the antibody would perform in cancer patients," says John Laterra, co-director of the Brain Cancer Program at the Johns Hopkins Kimmel Cancer Center and professor of neurology at Johns Hopkins University's School of Medicine. "But the study points the way toward targeting this key channel in human cancers, particularly since KCNK9 is overexpressed in about 40 percent of breast and lung cancers."

Y4 was developed in the laboratory by injecting mice with a human version of the KCNK9 protein. When the researchers added Y4 to lab-grown human breast cancer and lung cancer cells that expressed KCNK9, the antibody reduced the cells' growth by between 25 to 65 percent. It also triggered cell death in three of the cancer cell lines by between 5 and 30 percent.

In further tests of the antibody, scientists found that Y4 could slow the growth of human lung cancer cells transplanted into mice by up to 70 percent. The antibody did not completely halt tumor growth or shrink existing lung cancer tumors. However, in mice injected with mouse breast cancer cells, the antibody decreased the number of lung metastases from an average of 30 metastases to an average of five after 25 days of treatment.

The more KCNK9 is expressed in a tumor, the poorer the survival rates for lung and breast cancer patients, Laterra and colleagues observed. KCNK9 expression is not routinely measured in cancer patients, Laterra says, but he believes that if his study results are confirmed, such testing should be considered.

"We've generated a fair amount of evidence that targeting this channel alone can have antitumor effects," Laterra says. "We are now establishing more data on other common tumor types to find out what percentage are expressing this channel at levels that we feel would be sufficient to propose blocking the channel therapeutically one day."

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