Research Enables Safe Cancer Treatment, Toxicity-Free Immunotherapy

A recent article published in the science journal Nature Biotechnology showcased a scientific marvel. Researchers from the Massachusetts General Hospital have struck gold in evolving immunotherapy to better fight against tumors and cancers.

The research team had a particular case of glioblastoma to work on. Glioblastoma is the most common brain cancer these days. Cancer lays down its own blood supply to feed the tumor which can then grow uncontrollably and that characteristic makes it all the more deadly.

The technique used by the researchers proved to be very successful against brain cancer and could prove very beneficial in treating other solid tumors.

The research team took T-cells from the patient and modified them genetically to recognize the particular kind of tumor they had to fight. They did this by allowing the T cells to identify antigens on the tumor surface.

Once the cells were ready, they were returned to the patient’s body where they can carry out their noble work. It is notable that as this technique activates the body’s immune system against cancer, it is least dangerous.

The research team has named this treatment as the Chimeric Antigen Receptor T -cell (CAR T) therapy.

The team sought the approval of FDA for two commercial products which will employ the CAR T therapy to fight the deadly cancers of the lymphatic system and blood namely the non-Hodgkin lymphoma and acute lymphoblastic leukemia, respectively.

It is a known fact that the blood vessels in the region of the brain do not allow conventional cancer treatment drugs to pass through, hence treatment using them is largely ineffective. Any solid tumors such as these would have the same barrier.

Dr. Marcela V. Maus, MD, Ph.D. was the lead researcher on the team. Mr. Maus serves as the director of cellular immunotherapy at the MGH Cancer Center and as an assistant professor of medicine at Harvard Medical School (HMS).

“We previously made CAR T cells for glioblastoma, and one of the challenges of glioblastoma is that not all of the tumor cells express the target that a T cell can go after,” says Maus.

The team targeted the common surface protein which is found across most, if not all, cancers namely the EGFRvIII. This variant III is the receptor associated with the epidermal growth.

The principal problem faced by the team in targeting the EGFR was that it is found across many cells in the body in different regions. They had to make sure that the CAR T cells perform their desired function and at the same time does not affect the other regions of the body.

To circumvent the problem of the drug targeting non-cancerous cells the team made a system whereby the CAR-Ts were directly delivered to the cerebrospinal fluid around the hindbrain.

Once inside the brain, the CAR-Ts begin the second phase of immunotherapy by producing a T-cell engager which is a kind of guidance system that guides the T cells to target the affected cells.

The T-cell engagers which are produced in the process are antibodies that direct the ‘live’ T cells to the killing sites. These antibodies are called the bi-specific T-cell engager, or “BiTE.” for short.

BiTEs also fall under the same category of substances that are unable to cross the brain-blood barrier but that the team used this limitation to their advantage. The team said that the BiTEs manufacturing CAR-Ts which they inject do not affect the other regions of the body because they cannot enter the blood freely.

Dr. Maus said, “These CAR-Ts have a local tumor effect by targeting the second antigen, and that’s a way of overcoming this tumor heterogeneity and being able to target two things at once. But because it’s produced on the other side of the blood-brain barrier and in small quantities, it doesn’t cause the toxicities to other organs,”.

On the test subject, the technique yielded a greater than 80% success rate in eliminating the tumors.

The greatest issue at hand currently is the finances which will be required to make this technology easily accessible and market-ready.

Adeena Tariq

Adeena's professional life has been mostly in hospital management, while studying international business in college. Of course, she now covers topics for us in health.

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