The great promise of immunotherapy to fight cancer has not been fully realized. However, this could soon change thanks to a new discovery. By learning how to harness the body’s immune system, Weizmann researchers are paving the way to new treatments for cancer and autoimmune diseases.
When it comes to the battle against cancer, the immune system’s soldiers (called T cells) quickly become exhausted, and branch-like (dendritic) cells that communicate with other cells are scarce. This is one reason why many cancer patients experience a recurrence even after the primary growth has been removed and metastases have been treated. Often, tiny remnants of the disease escape detection and start developing later, causing the tumor to recur.
Researchers from the laboratories of Dr. Rony Dahan and Prof. Ido Amit in the Systems Immunology Department set out to learn why existing treatments fall short. The researchers examined almost 130,000 T cells, some of which responded to the treatment and some of which did not.
“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,” Prof. Amit explains.
Dendritic cells collect intelligence from malignant cells, then deliver that information to T cells, warning them about the cancerous growth and prompting them to take action. But when the researchers examined a cancer model, they discovered that the relevant population of dendritic cells is rarely present in most cancerous growths and in most patients currently being treated with an existing antibody therapy.
This understanding paved the way for engineering a new antibody called Bispecific DC-T Cell Engager (BiCE), which has two arms. One arm binds to T cells, just as existing treatments do, but the other arm recruits dendritic cells from the rare population to activate T cells. The development of the new treatment was led by doctoral research students Yuval Shapir Itai, from Dr. Dahan’s laboratory, and Oren Barboy, from Prof. Amit’s laboratory.
The researchers discovered that the cellular pairs created by the BiCE antibody triggered an immune response against cancerous growth. 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 T cells there, sharing intel and activating them.
The creation of BiCE and the researchers' other findings open a new avenue in developing treatments that link various cells in the immune system. “This development,” Dr. Dahan said, “gives hope not only to cancer patients, who need to have their immune systems activated to fight off the growth, but also to people with other diseases such as autoimmune diseases."
Yeda Research and Development, which is responsible for commercializing the intellectual property of Weizmann Institute scientists, has filed a patent application and is working to develop an innovative treatment based on the BiCE antibody created in a Weizmann lab.