Targets on the horizon: Emerging therapies and nov...(or growth in mouse models of breast colo...),Health

While tumors can present markers that indicate they are diseased, they often evade the innate immune system by producing an excess of CD59, a surface protein that prevents the assembly of complement proteins on the outside of tumor cells, said Baldwin Mak, Ph.D., a research scientist at ARIUS. Through the inhibition of CD59, we can disrupt a cancer cells ability to keep the immune system from poking holes in its membrane.

According to Mak, the CD59-inhibiting antibody was discovered through a technique developed at ARIUS called FunctionFIRST™, a methodology that screens antibodies for cell killing effects rather than creating antibodies that bind a specific target. After AR36A36.11.1 proved effective at killing cultured cancer cells, the researchers tested the molecule in animal models of adenocarcinomas. Subsequent analyses revealed the mechanism of action the antibody binds to a region on CD59 that inhibits formation of membrane attack complexes, which form pores that cause cell lysis, said Mak.

When administered in mice once a week for eight weeks, AR36A36.11.1 inhibited breast cancer tumor growth by 100 percent. Mouse studies also revealed that the antibody could halt the growth of prostate tumors by 86 percent, lung tumors by 58 percent and colon tumors by 48 percent, said Mak.

Our studies seem especially promising in breast cancer models, where CD59 inhibition by the antibody appears to cause complete tumor regression at all dose levels, said Mak. In particular, this potent effect is observed in a breast cancer model that represents a patient population that cannot be treated by Herceptin, the only therapeutic antibody approved for breast cancer treatment.

A humanized AR36A36.11.1, suitable for clinical studies, has been made and the researchers are preparing to test this antibody in clinical trials.