Weizmann Institute scientists discovered a survival mechanism of blood cancer cells, and managed to block it with antibodies

This discovery, recently published in the scientific journal PNAS, may form the basis for the development of advanced treatment methods for the disease

Blood cancer of the type called chronic lymphocytic leukemia is characterized by the accumulation of a certain type of white blood cells, called type B lymphocytes, in the blood, bone marrow and lymph nodes. Normally, the lifespan of blood cells is limited by an internal mechanism that causes self-killing. In cancer cells, this destruction mechanism does not function properly, so the cells survive, multiply and accumulate. A group of scientists led by Prof. Idit Shahar from the Department of Immunology at the Weizmann Institute of Science, in cooperation with Dr. Michal Haran and the team of the Hematology Institute at the Kaplan Medical Center, recently discovered an important survival mechanism of these cancer cells. Through a deliberate and focused injury to the survival mechanism, the scientists were able to cause their increased mortality. This discovery, recently published in the scientific journal "Records of the National Academy of Sciences of the United States of America" ​​(PNAS), may form the basis for the development of advanced treatment methods for this disease, and possibly also for other diseases in which there is an accumulation of type B white blood cells.

Previous studies by Prof. Shahar showed that a certain receptor, found on the surface of normal B cells, plays an important role in the survival of these cells. In light of this, the possibility was raised that this receptor is also involved in the abnormal survival of malignant cells of the same type.

The members of Prof. Shahar's research group, including the research students Inbal Binsky, Diana Strelts, Yael Gor and the laboratory technician Frida Lantner, together with a team of doctors from the Hematology Institute at the Kaplan Medical Center in Rehovot, which included Dr. Haran, Dr. Lev Shoidal, Prof. Alan Barbie and Nurit Harpaz, scientists from Yale University and Dr. David M. Goldenberg from the Department of Immunology and Molecular Medicine at the New Jersey Cancer Research Center, tested cancerous blood cells taken from patients with chronic lymphocytic leukemia, and discovered that these cells contain high levels of both the receptor and the protein that binds to it, starting from the early stages of the disease. It later became clear that the activation of the receptor leads to a sequence of intracellular events, which increases the ability of the cancer cells to survive. One of the most important steps in the process is a significant increase in the production of a substance that regulates the lifespan of blood cells. This substance causes the production of a protein that prevents the activation of the self-destruction program. When the cancer cells were treated with antibodies that bind to the receptor selectively, and inhibit its activation, there was a significant increase in the death of the cancer cells. These antibodies, produced by the company Immunomedics in New Jersey, are currently in the first phase of clinical trials for the treatment of various types of cancer. The research findings provide an explanation for their mechanism of action, and following it a clinical study is planned to test the effectiveness of the antibodies among patients suffering from chronic lymphocytic leukemia.

Prof. Shahar: "We believe that the abnormal amounts of the receptor play an important role in the development of the disease, starting from the early stages, and that they are responsible for the increased survival of type B cancer cells. Blocking the receptor, or other stages in the survival pathway it activates, may be used in the future as a means Effective for fighting other types of cancer, which originate from type B blood cells."