(l-r) Dr. Rony Dahan, Yuval Shapir Itai, Oren Barboy and Prof. Ido Amit (Weizmann Institute of Science)
Scientists from Israel’s Weizmann Institute of Science developed a new antibody that they say connects T cells to dendritic cells, thereby creating a powerful immune response to cancerous growths. This, they say, is a breakthrough that could lead to new treatments for cancer and autoimmune diseases.
The Cleveland Clinic explains that T-cells are a type of white blood cell called lymphocytes. They help your immune system fight germs and protect you from disease. There are two main types. Cytotoxic T-cells destroy infected cells. Helper T-cells send signals that direct other immune cells to fight infection.
Your lymphocytes include T-cells and B-cells. Both types are part of your body’s defense. B-cells make proteins called antibodies to fight pathogens. T-cells protect you by destroying harmful pathogens and by sending signals that help control your immune system’s response to threats.
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The Weizmann Institute scientists explain that one of the most prominent immunotherapies makes use of antibodies that block PD-1, a regulatory “checkpoint” receptor found on the surface of T cells. When this receptor is expressed in T cells, a protein widespread in the tumor environment can attach to it, switching the T cells into a state known as exhaustion. PD-1 antibodies prevent this protein from attaching to T cells and repressing them, but many cancer patients fail to respond to this treatment; in many others, the effectiveness is short-lived.
To develop a more effective immunotherapy, researchers from the laboratories of Dr. Rony Dahan and Prof. Ido Amit in Weizmann’s Systems Immunology Department started by asking why existing treatments fall short. To answer this question, they sampled T cells from two mouse models of cancer that had undergone PD-1 antibody treatment. “Using advanced technologies such as single-cell DNA sequencing and big data algorithms, we examined almost 130,000 T cells, some of which responded to the treatment and some of which did not,” Amit explained. “Surprisingly, the group of T cells that did respond to the treatment expressed genes pointing toward an interaction with a rare population of dendritic cells.”
Having created their antibody, the researchers studied its mechanism of action. When they used fluorescent markers to label the antibody and the immune cells of mice with skin cancer who had been given the new treatment, they were able to observe how the antibody physically connects the T cells to the dendritic cells, increasing the number of such cellular pairs around the cancerous growth and in the adjacent lymph nodes. They also discovered that the cellular pairs created by the antibody were active and that they triggered an immune response against the growth. Moreover, in the wake of the treatment, the dendritic cells that had been adjacent to the cancerous growth migrated to the lymph nodes and connected to the T cells there, in order to share intel and activate them.
