Engineered Antibody System to Kill Cancer Cells

Catharine Paddock Ph.D. composed an article that was fact-checked by Jasmin Collier about an engineered antibody that summons the immune system to kill cancer cells. It attaches itself to the cancer cells before summoning and activating the killer T cells from the immune system to destroy them.

The body can be protected in many ways by the immune system against cells that grow out of control. There are times though when the rogue cells evade these natural defenses and aid cancer. Immunotherapy is developing therapies that can give our immune system a big helping hand.

The Scripps Research Institute researchers in Jupiter, Fl, and the National Heart, Lung and Blood Institute of the National Institutes of Health in Bethesda, MD, have now engineered a form of a “two-pronged” anti-cancer antibody.

The first prong helps the antibody to locate a unique protein that is called receptor tyrosine kinase (ROR1) that is present on the surface of cancer cells but not healthy cells. The antibody binds to the cancer cell when it finds the protein and effectively turns it into a target.

The second prong attracts and binds to killer T cells, which are a type of white blood cell in the immune system that kills all of the cells that pose a threat. The killer T cell is then activated to release toxins that destroy the cancer cell.

Scientists reported how they engineered and tested their T cell engaging bispecific antibody in a paper published in the Proceedings of the National Academy of Sciences.

Senior study author Christoph Rader, an associate professor at The Scripps Research Institute explains that “once the T cells are recruited and activated, they release cytotoxic molecules that penetrate the target cells and kill them”. He also explains that natural antibodies can’t do this and you have to engineer them in a bi-specific fashion in order to do so.

White blood cells make up the antibodies that are proteins. When they patrol the bloodstream seeking bacteria, viruses and other non-self substances and have found their target, they bind to them. This is a well-established field of treatment and there are many approved antibody-based molecules. The challenge is to find a protein target that is specific to cancer cells so the healthy cells do not get caught up in the battle.

Much of the work was carried out first by Dr. Junpeng Qi, a research associate in Prof. Rader’s group that involved the creation of a bi-specific antibody that remains active for days. But the single bi-specific antibody that has received regulatory approval in the U.S. only remains active for a few hours.

The antibodies need to stay in the blood longer, but not ideal to linger for too long in order to avoid toxic side effects. The unique aspect of this bi-specific antibody is that it can work in many different cancer indications.

Dr Fredda Branyon