The first antibody treatment against a variety of human solid tumors
Science wins a new battle in the war against cancer
A study from the Stanford University School of Medicine has recently shown that a newly discovered antibody, the anti-CD47, can unhide the cancer cells, making them visible and vulnerable to the action of the immune system.
CD47 (Cluster of Differentiation 47) is a protein encoded in humans by the CD47 gene, which functions as a “don’t eat me” signal for phagocytic cells. Phagocytic cells are cells that engulf and absorb waste material, harmful microorganisms, or other foreign bodies in the bloodstream and tissues.
Scientists observed that CD47 is used by some cancer cells to hide from normal scavenging by macrophages. According to a new study from the Stanford University School of Medicine, a newly discovered antibody, the anti-CD47, unhide the cancer cells, making them visible for macrophages and other cells in the immune system. This seems to be the first antibody treatment shown to be broadly effective against a variety of human solid tumors.
“Blocking this ‘don’t-eat-me’ signal inhibits the growth in mice of nearly every human cancer we tested, with minimal toxicity,” said professor of pathology Irving Weissman, MD, who directs Stanford’s Institute of Stem Cell Biology and Regenerative Medicine and the Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford. “This shows conclusively that this protein, CD47, is a legitimate and promising target for human cancer therapy.”
The conclusion of the study conducted by Weissman comes after more years of researches. Initially, in 2010, Weissman and his coleagues found that blocking CD47 with a specific antibody can cure some cases of human non-Hodgkin’s lymphoma in mice. Continuing their study, they showed that nearly every human cancer cell expressed CD47 — usually at higher levels (on average, about three times more) than did non-cancerous cells and inhibiting these signals can determine the macrophages to attack the cancerous cells.
“The anti-CD47 antibodies can dramatically inhibit the growth of human solid tumors by blocking the ability of CD47 to transmit the ‘don’t-eat-me’ signal to macrophages,” concluded Weissman and his colleagues. “If the tumor was highly aggressive, the antibody also blocked metastasis. It’s becoming very clear that, in order for a cancer to survive in the body, it has to find some way to evade the cells of the innate immune system.” The innate immune system is the body’s first line of defense against pathogens like bacteria and viruses. Unlike the adaptive immunity conferred by antibodies and T cells that recognize and battle specific molecules, cells of the innate immune system, like macrophages, respond non-specifically to a variety of threats.
Unfortunately, the researchers’ approach didn’t work for every type of cancer and for every animal implied in the study. A set of mice with breast cancer cells from one human patient experienced no benefit from antibody treatment. The researches have recognized that it is highly imperative to learn more about the relationship between macrophages and tumor cells, and how to draw more macrophages to the tumors. Their further studies are focused on curing cancer by reducing the size of a tumor with surgery or radiotherapy before the antibody treatment to make it the more effective. Another solution analyzed by Weissman would be the use a second antibody in addition to CD47 to further stimulate the ability of the macrophages or other immune cells to kill the cancer cells.
Eager to win the war against cancer, Weissman declares: “We believe these results show that we should move forward quickly but cautiously into human clinical trials for many types of solid tumors”.
”The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors”- Stephen B. Willinghama, Irving L. Weissmana and colleagues, PNAS, 2012;