Researchers may have found an anti-cancer treatment that overcomes cancer's tricky evasion of the human immune system. Cancer can elude the immune system by fooling white blood cells into not attacking and not eating away overgrown tumors.
Stanford University School of Medicine researchers developed an antibody which masks a flag that tumors wave as a don't eat me signal. The result? Tumors become immune targets anew, according to a study published in the journal the Proceedings of the National Academy of Sciences on Monday.
This is exciting work and will surely trigger a worldwide wave of research designed to convert this strategy into useful therapies, Robert Weinberg, a biology professor at the Whitehead Institute for Biomedical Research unaffiliated with the study, said in a statement. Mobilizing the immune system to attack solid tumors has been a longstanding goal of many cancer researchers for decades.
The researchers injected mice that had transplanted human tumors with an antibody that blocks a protein called CD47, which prompts macrophage cells that attack and eat threats inside the body to release a cell that it has grabbed. Normally this mechanism is used so that the immune system doesn't accidentally destroy normal cells, but cancer exploits this natural defense
But when CD47 was covered up by the antibody, cancer growth diminished.
While the antibody inhibited the growth and spread of the cancers in the mice tested, the issue is whether targeting CD47 alone will have efficacy in human cancers, says Ravindra Majeti, one of the study's authors.
The other possible problem is that masking CD47 on non-cancerous cells will likely muck up the body's ability to shield other, normal cells from being destroyed by the immune system. Healthy red blood cells, for instance, also use CD47 to tell the ever-hungry macrophages lurking in the bloodstream not to eat them by mistake.
Majeti says the Stanford group is already moving to test the CD47 antibodies in human subjects. Thanks in part to a grant from California Institute for Regenerative Medicine, the researchers have enough funds to bring the treatment up to Phase I of clinical testing, which will determine if the antibody is safe enough to test as a therapy.
Researchers previously knew that certain types of cancers, such as bladder cancer, use CD47 to hide from the immune system. But the Stanford scientists showed that tumor cells collected from patients with ovarian, breast, colon, and prostate cancer, among others, expressed CD47 as well, and that tumor cells expressed CD47 at an average of more than three times the rate of normal cells.
A higher rate of CD47 expression levels also correlates with lower survival rates for patients with ovarian cancer and certain kinds of brain and spine tumors, according to the study.
Antibody treatments for a range of diseases are already a booming business - about $20 billion dollars a year in sales, according to Majeti.
The U.S. Food and Drug Administration already approved 12 antibody treatments for solid tumors and cancers of the blood, bone marrow and lymph nodes, according to a review article published last week in Nature Reviews Cancer.
Existing antibody cancer treatments include various targets. Cetuximab, sold commercially in the U.S. by Eli Lilly & Co. subsidiary ImClone under the name Erbitux, blocks a receptor that allows some colorectal and head and neck cancers to grow uncontrollably. Another treatment, rituximab, targets a protein primarily found on the surfaces of B cells and is used to treat lymphoma, leukemia and other blood and bone marrow cancers that are caused by patients with excess or dysfunctional B cells.
The success of the CD47 antibody shows that we should move forward quickly but cautiously into human clinical trials for many types of solid tumors, senior author Irving L. Weissman said in a statement.