SAEDNEWS: Researchers say this new method may help treat patients with certain cancers with minimal side effects.
According to SaedNews, for some proteins, a single mutation or change in DNA instructions can mean the difference between normal function and cancer formation.
Despite causing significant diseases, these mutated proteins can be so similar to their normal versions that treatments targeting these mutations also harm healthy cells.
A new study by researchers from NYU Langone Health and the Perlmutter Cancer Center describes the development of a biologic drug derived from natural biological systems. This drug targets a mutated cancer protein called Human Epidermal Growth Factor Receptor 2 (HER2) without attacking its nearly identical natural counterparts in healthy cells.
While still in its early stages, researchers say this approach could lead to new treatments for cancer patients with HER2 mutations with minimal side effects.
Shohei Koide, the lead researcher, says: "We aimed to create an antibody that could detect a single change in the 600 amino acid building blocks that make up the exposed part of the HER2 protein, something considered very challenging."
The fact that we could detect the difference of a single amino acid so precisely was astonishing.
When an amino acid change locks a protein in an "always on" state, it can cause cancer by leading to uncontrolled cell division and proliferation.
Several FDA-approved treatments, including trastuzumab and pertuzumab, can treat these types of cancers. However, these treatments work at the cellular level where only low levels of the mutated HER2 protein occur.
Dr. Koide, Director of Cancer Biologics, says: "This means we can't just mark cancer cells by looking at HER2 levels."
Moreover, since some approved treatments can't distinguish between mutated and normal HER2, they are likely to harm healthy cells expressing normal HER2.
Antibodies are large, Y-shaped proteins that bind to specific targets and signal immune cells.
In a process similar to natural antibody development, researchers exposed antibodies to several rounds of mutation and selection, seeking variants that recognized mutated HER2 but not the normal version.
By capturing atomic images using cryo-electron microscopy, the team observed how their new antibodies spatially interacted with HER2.
However, selectively identifying mutated HER2 versions was only part of developing an effective cancer treatment, as antibodies must work with the immune system to kill cancer cells.
