Glowing antibodies
A new method of antibody modification will help in the detection and treatment of tumor diseases
Russian scientists have developed a new method for producing luminous antibodies that can be used to detect cells with a specific pathological protein, such as tumor cells. The method proposed by the authors, unlike the classical ones, is easy to use and can be applied to any immunoglobulins. In the future, it may be useful not only in diagnostics, but also for targeted drug delivery. The study was supported by a grant from the Russian Science Foundation (RNF) and published in the International Journal of Molecular Sciences (Sapozhnikova et al., Sensitive Immunofluorescent Detection of the PAME Antigen Using a Practical Antibody Conjugation Approach).
In a number of pathological processes, especially those associated with the development of cancerous tumors, specific proteins appear on the surface of defective cells. It is with their help that it is possible not only to detect signs of a dangerous disease in the patient's biological samples, but also to organize targeted drug delivery. Special proteins — monoclonal antibodies - help in all this. They are isolated by immune cells to fight potentially dangerous objects, or antigens. Sewing various molecules to antibodies, for example glowing or with a drug, has already become quite a routine approach.
"Stained monoclonal antibodies are a promising tool for cancer diagnosis due to their high brightness, specificity and stability. However, there is a problem: most methods use low—stable forms of dyes," said young scientists of the Institute of Bioorganic Chemistry named after Academicians M. M. Shemyakin and Yu. A. Ovchinnikov (Moscow) Vladimir Brylev and Ksenia Sapozhnikova.
The researchers proposed a simple method of fluorescent modification of the most common antibodies — immunoglobulins G. The antibody has a Y-shaped shape: a "trunk" and "branches" binding antigens, which it is important not to touch when sewing on the dye. The authors concentrated on the "trunks", namely, the residues of sugars — glycans associated with them, which were oxidized according to the classical method with the formation of aldehyde groups. Protected stable derivatives of dyes have also been obtained, which can be easily converted into a chemically active form. These substances selectively react with aldehyde groups of oxidized antibody sites under mild conditions as a result of so-called "oxime ligation", but they can be stored indefinitely.
In this way, scientists prepared antibodies to a protein that manifests itself in tumors (mainly melanoma), and tested them to detect cancer cells in a culture mixed with normal ones, as well as in bone marrow samples of cancer patients. In both cases, the antibodies bound well to the desired cells, the glow was bright and persisted for a long time.
"With this work, we have proved that our antibody modification method is really effective. In the future, we plan to use the technology in the detection of socially significant diseases. First of all, these are oncological diseases; we also want to try out a technique for determining some microbial and viral infections. The developed modification method, due to its simplicity, can be used to obtain conjugates of immunoglobulins of various purposes, including therapeutic ones," the authors noted.
You can learn more about the work of researchers in a virtual tour of the laboratory, created by the Russian Science Foundation as part of the large-scale multimedia project "Science in 360° format".
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