The Science behind the Successful Pharma Deal

Kite Pharma, the manufacturer of an Israeli-research-based immunotherapeutic treatment, has been sold to the American pharmaceutical giant Gilead for 11.9 billion dollars in cash. The therapy is based on genetic engineering of a certain type of immune cells, called T cells, in order to instill them with the ability to specifically kill cancer cells without harming other cells in the body.

Kite Pharma is headed by Prof. Arie Belldegrun, an Israeli physician and scientist who has resided in the U.S. since the 1980s and serves as the company’s chair, president, and CEO. Belldegrun, an oncologist and urologist, studied medicine at The Hebrew University and continued his scientific and medical training at the Weizmann Institute of Science and Harvard University. He joined forces with an American researcher, Steven Rosenberg, in an attempt to enhance the activity of T cells, so that they are more effective in fighting cancer.

T cells are part of the adaptive immune system, the component of the immune system that learns to recognize potentially harmful invaders and attack them. Among their various roles, these cells are capable of destroying virus-infected cells and cancer cells. Belldegrun and Rosenberg found that it is possible to extract T cells from a patient, enhance their activity in the lab, let them replicate, and then inject them back into the patient. Since these are cells taken from the same person, the immune system will not attack them, as may happen when cells are grafted from another donor.

Specific compatibility

The disadvantage of this method was that the T cell enhancement was not specific enough – that is, they were not sufficiently efficient in fighting cancer. This is where the Weizmann Institute’s Prof. Zelig Eshhar comes in.

T cells use a receptor on their outer surface to recognize the cells they are supposed to destroy. The receptor binds to a specific protein on the outer surface of the target cell.

In his pioneer research, Eshhar developed a method to engineer the T cell receptor so that the region directed against the target cancer cell protein would be taken from an antibody specific to that protein. This increases the engineered cells’ specificity, turning them into effective machines that detect and destroy cancer cells. The technology was named Chimeric Antigen Receptor, or CAR (i.e., a chimeric receptor combining the original receptor and an antibody).

Now the researchers had the two components of a system capable of overcoming cancer: immune cells engineered to recognize cancer cells more effectively so that they attack only them; and methods for culturing the engineered cells in the lab in large numbers, so that they could be injected back into the patients.

The therapeutic technique has been successfully tested in clinical trials on blood cancers, such as lymphoma and leukemia. This treatment is especially effective against these cancers since T cells reside naturally in the blood and lymph vessels, and the cancer cells are scattered there, as opposed to being lumped up in a solid tumor with hard-to-reach internal layers. Ongoing trials are testing this treatment option in solid tumors.

The minds behind the success. Right to left: Eshhar, Rosenberg and Belldegrun | Photographs: Weizmann Institute of Science, Kite Pharma, NCI  

Anticipated approval

Kite Pharma’s leading product is called Axi-Cel, used to treat non-Hodgkin’s lymphoma. The product has yet to be approved by the FDA, which is tasked with approving clinically tested drugs for marketing, but it is expected to gain approval in November this year. This makes the company’s purchase even more impressive, and indicates that Gilead, as well as the entire market, has a lot of faith in the therapeutic technique.

When Belldegrun, Rosenberg, and Eshhar conducted their revolutionary experiments three decades ago, few believed the treatment would work; it sounded like science fiction. Evidently, it took many years to perfect the treatment and ensure its safety for use. This treatment is part of the immunotherapy revolution we are witnessing in cancer therapy in recent years, which is gradually moving from the laboratories and clinical trials into routine treatment in the health system, providing new hope for millions of cancer patients around the world.

Watch Kite Pharma's video about the CAR treatment:

Translated by Elee Shimshoni