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Cancer research: Proteins transport active substances to the cancer tumor

Cancer research: Proteins transport active substances to the cancer tumor


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Novelty in targeted cancer treatment

Classic chemotherapy is the only treatment for many cancers. The problem with therapy, however, is that the entire body is affected. A German research team now wants to significantly reduce the drastic side effects of this cancer treatment by converting proteins and antibodies into stable drug transporters that deliver the drug directly to the tumor cell without damaging other cells.

Researchers at the Leibniz Research Institute for Molecular Pharmacology (FMP) and the Ludwig Maximilians University in Munich (LMU) reached a new milestone in targeted cancer treatment. The team developed a novel technology that enables natural proteins and antibodies to be loaded with medicinal agents or fluorescent agents. These transporters are then supposed to bring the charge directly to the tumor cells and either kill or mark them. The research results were presented in the journal “Angewandte Chemie”.

Chemotherapy: painful healing

In the classic treatment of cancer with chemotherapy, toxic substances are introduced into the body. Rapidly dividing cancer cells are particularly sensitive to these toxic substances and die faster than healthy tissue. However, such therapy does not remain without damage to healthy cells, which is why there are considerable side effects. In addition, chemotherapy is not suitable for all types of cancer, since in some cases the toxic concentration required would be too high to be expected by people who are ill.

Targeted cancer treatment is intended to replace chemotherapy

For this reason, scientists are researching ways of delivering active substances in the body to the place of use. There are currently five so-called antibody drug conjugates (ADCs) on the market. In this method, antibodies are linked to active substances that can detect cancer cells and then use the active substance in a targeted manner. The problem, however, is that the available ADCs often lose their charge beforehand and release it in the bloodstream.

Lower dose and reduced side effects

The research team led by Professor Christian Hackenberger and Professor Heinrich Leonhardt has now been able to fulfill the request for more stable drug transporters for cancer treatment. This paves the way for cancer therapies with lower doses and side effects. "We have developed a new type of technology that enables natural proteins and antibodies to be linked to complex molecules such as fluorescent dyes or medicinal agents, and is easier and more stable than ever before," explains Marc-André Kasper from the research team.

Phosphorus molecules as stable drug transporters

The researchers found that unsaturated phosphorus (V) compounds (phosphonamidates) are ideal for this task. These phosphonamidates are able to bind active ingredients or other desired substances via the rare amino acid cysteine. Since cysteine ​​is rarely found in the body, the protein can be controlled very well, according to the study. In addition, the active ingredients were very easy to incorporate into the molecules. "The greatest achievement of the new method, however, is that the resulting bond is stable during circulation in the blood," emphasizes Kasper. The ADCs available today could not do this.

Initial tests showed amazing results

The research team compared the new phosphor transporters with the already approved ADC Adcetris®. In the blood serum, the researchers were able to document how the new phosphorus compounds could hold the active substances better for days. In experiments on mice with Hodgkin's lymphoma, the phosphonamidate-linked drug transporters also proved to be more effective. "The technology therefore has great potential to replace common methods in order to develop more effective and safe ADCs in the future," summarizes group leader Christian Hackenberger. In the next step, the new drug transporters will be tested on humans. (vb)

Author and source information

This text corresponds to the requirements of the medical literature, medical guidelines and current studies and has been checked by medical doctors.

Graduate editor (FH) Volker Blasek

Swell:

  • Leibniz Research Institute for Molecular Pharmacology Bringing cancer medication safely to its destination (accessed: 08.08.2019), leibniz-fmp.de
  • Kasper, Marc ‐ André / Glanz, Maria / Stengl, Andreas / u.a .: Cysteine ​​‐ Selective Phosphonamidate Electrophiles for Modular Protein Bioconjugations, Angewandte Chemie International Edition, 2019, onlinelibrary.wiley.com
  • Kasper, Marc ‐ André / Stengl, Andreas / Ochtrop, Philipp / et al .: Ethynylphosphonamidates for the Rapid and Cysteine ​​‐ Selective Generation of Efficacious Antibody – Drug Conjugates, Angewandte Chemie International Edition, 2019, onlinelibrary.wiley.com



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