A target for killers
The immune system usually protects the body from the tumor. But sometimes cancer cells suppress it or hide from this complex defense. At the Scripps Research Institute in Florida, scientists led by Christoph Rader have developed a new type of anti-cancer antibodies that can enhance the body's fight against cancer by delivering T-killers directly to cancer cells.
These bispecific antibodies attach themselves to malignant cells with one part, and with T–killers with the other, which attack the labeled targets, leaving healthy cells intact. The selective effect is due to the specific targeting of the ROR1 protein found on the surface of several types of cancer cells.
Bispecific antibodies are a Y-shaped immune factor capable of binding to both a specific target and T-killers. When the T-killers attracted to the target accumulate in the tumor and are activated, they release cytotoxic molecules that penetrate the malignant cells and kill them.
Rader and his colleagues were particularly interested in the use of bispecific antibodies to HER2-negative breast cancer, which does not respond well to treatment. The expression of ROR1 in HER2-negative breast cancer is usually elevated.
The ROR1 protein is a convenient target for fighting cancer, it is present only in mature malignant cells. ROR1 was first detected ten years ago in leukemia.
Structure of the ROR1-binding arm of a bispecific antibody in complex with ROR1
it was determined by X-ray crystallography.
ROR1 is normally expressed during embryonic development. After birth, its synthesis stops and resumes with oncological diseases of the blood and other malignant neoplasms, including lung, breast and ovarian cancer.
Bispecific antibodies in the experiment with animal models remained active for five days – this is a good achievement compared to modern approaches. Thus, the only FDA-approved bispecific antibody that fights acute lymphoblastic leukemia is active for only a few hours.
To create bispecific antibodies, the authors used components of natural antibodies, which gave a large size and the ability to recycle and stay in the blood longer. But eventually the body gets rid of them – this reduces the risk of systemic toxic effects.
Article by J. Qi et al. The potential and selective antitumor activity of a T cell-engaging bispecific antibody targeting a membrane-proximal epitope of ROR1 is published in the journal PNAS.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of The Scripps Research Institute: Two-pronged antibodies draw immune killers directly to cancer cells.