Researchers from The Scripps Research Institute in Florida and the National Heart, Lung, and Blood Institute of the National Institutes of Health in Maryland recently announced they had engineered a new kind of antibody that attaches to cancer cells and then calls T cells to come and kill the cancer cells. This is one of the latest immunotherapy approaches taken to boost the body’s own immune system response to fight cancer.
The research findings were published in the Proceedings of the National Academy of Sciences on May 29.
Two-pronged anti-cancer antibody
This new genetically engineered antibody features two prongs with different jobs. The first prong helps the antibody locate a unique protein call receptor tyrosine kinase ROR1. This protein is found on the surface of cancer cells, but not on healthy cells.
When the antibody finds ROR1, it binds to the cancer cell housing the protein. When this happens, the cancer cell can now become a target.
That’s where the second prong comes in. The second prong of the antibody attracts the body’s famed killer T cells to the marked cancer cells. T cells are a type of white blood cell in the immune system that kills invading cells. When the T cells come into contact with the cancer cells with the ROR1, they release toxins to destroy the cancer cell.
Need for an engineered antibody
In the paper, the scientists reported how they engineered and tested this new antibody. The antibody had to be engineered to attract T cells to the cancer cells to which the antibody bound itself.
“Once the T cells are recruited and activated,” Christoph Rader, an associate professor at The Scripps Research Institute, and senior study author, writes, “they release cytotoxic molecules that penetrate the target cells and kill them.” The paper notes that the body’s natural antibodies cannot do this; that’s why the researchers genetically engineered them to have this two-pronged capability.
Immunotherapy is being studied extensively as a new approach to attack cancer. Antibodies do the work currently trusted to drugs (chemotherapy) or radiation. Antibodies are proteins made by the white blood cells. They course through the bloodstream seeking viruses, bacteria, and other foreign substances. Once they find an invader, they attach to the cells and kill them.
In this case, the antibodies can bind to two targets, the protein-holding cancer cells and the T cells.
Tyrosine kinase ROR1 was chosen as the target because it “is expressed by numerous cancers and is largely absent from postnatal healthy cells and tissues.” Evidently ROR1 occurs in cells during the early stages of fetal development, but then goes away after birth.
In later years, ROR1 returns in cancer cells. ROR1 has been found on the surface of breast, lung, ovarian, and blood cancers, the study notes. This is especially relevant for HER2-negative breast cancer. “If you look at ROR1 expression in breast cancer,” the study notes, “you see that the patients who are HER2 negative are often ROR1 positive.”
The ROR1-attaching antibody has great potential Dr. Rader notes, “One of the most unique aspects of this bi-specific antibody is that it can work in so many different cancer indications.”