Single antibody developed by CIRM grantee fights many tumors

Stanford researcher Irv Weissman made the news yesterday when he published a paper showing that  a single antibody-based therapy can effectively slow the growth and in some cases eliminate many different kinds of human tumors, at least in mice.

Weissman leads a $20 million CIRM disease team that is developing an antibody-based therapy to treat leukemia. In previous work, Weissman had found that leukemia cells evade the immune system by placing a protein on their surface that tells the immune system “don’t eat me.” Blood-forming stem cells in the bone marrow also use that protein on occasion to avoid immune detection, as do red blood cells.

Weissman and his group are developing an antibody that latches onto that protein, called CD47, and makes the protein invisible to the immune system, particularly immune cells called macrophages. Without their “don’t eat me” signal, the macrophages ingest the leukemia cells.

Now, it looks as if that antibody therapy might be effective for cancers in addition to leukemia. Weissman and his group published a paper March 26 in the Proceedings of the National Academy of Sciences showing that CD47 is present at high levels on the surface of tumor samples taken from people with ovarian, breast, colon, bladder, brain, liver and prostate cancers.

What’s more, their antibody therapy prevented the growth of those tumor cells that had been implanted in mice, and in some instances eradicated them. A story in the Los Angeles Times describes the work:

Placing the cells in lab dishes, the team administered an antibody: a protein that binds to CD47 and blocks it from warding off immune system cells. Macrophages ate the cells.

The researchers then implanted human tumor cells in mice for further study. They allowed the cancers to grow, and administered the antibody against CD47.

Antibody treatment inhibited the growth of almost all of the solid tumors and was able to wipe out some smaller cancers altogether, according to the report, which was published Monday in the journal Proceedings of the National Academy of Sciences.

A press release from Stanford quotes Weissman:

“Blocking this ‘don’t-eat-me’ signal inhibits the growth in mice of nearly every human cancer we tested, with minimal toxicity. This shows conclusively that this protein, CD47, is a legitimate and promising target for human cancer therapy.”

A story in Science quotes Weissman talking about testing the drug in human trials:

Weissman's team has received a $20 million grant from the California Institute for Regenerative Medicine to move the findings from mouse studies to human safety tests. "We have enough data already," says Weissman, "that I can say I'm confident that this will move to phase I human trials."

A.A.