Researchers Alter Proteins to Treats Cancer Effectively

In a recent research at the Leibniz-ForschungsinstitutfürMolekularePharmakologie (FMP) and the Ludwig-Maximilians-Universität München (LMU), researchers developed an innovative technology aimed to treat cancer more effectively and with greater selectivity, without harming the normal cells.

The technology involves the transformation of proteins and antibodies into stable compounds for targeted drug response, achieved by the use of highly functional drugs transporters thus enabling the detection and destruction of tumors.

A common treatment of cancer is Classic chemotherapy that targets the rapidly dividing cells but accompanied by severe side effects due to their toxic composition.

A toxic dose can only effectively remove the tumor which is hazardous to the patient. However, prevailing research has introduced Antibody Drug Conjugates (ADCs) which selectively transport the active ingredients of the drug targeted specifically to the tumor cells.For instance, by the interaction of the active agents of the drug with an antibody cancer cells are detected. Five such ADCs are available in the market.

One of the drawbacks of ADCs is the release of their toxic composition on the way to their target cells. ADCs may cause devastating side effects as they cause the release of toxic agents into the bloodstream.

A team led by Professor Christian Hackenberger from the FMP and Professor Heinrich Leonhardt from the LMU Biocenter—ponder over the issue and discovered that these side effects can only be reduced with a highly stable and controlled interaction between the drug and antibody, these findings are published in journal AngewandteChemie.

A new drug transporter has been discovered with lesser side effects as the active agents work effectively at low doses.

Marc-André Kasper, a researcher in Christian Hackenberger’s group said: “We have developed an innovative technology that makes it possible to link native proteins and antibodies to complex molecules, such as fluorescent dyes or drugs more easily and with better stability than ever before,”

The exceptional properties of unsaturated phosphorous (V) compounds were investigated and disclosed by the researchers, which gave the opportunity of binding the active agents of the drug specifically to the cancer cells. The phosphorus compounds bind tremendously to cysteine amino acid in the antibody.

The naturally occurring amino acid, cysteine, has enabled drug conjugation by effective modifications per protein molecule. Added into that, the phosphorous compounds effectively form the conjugated compound.

The ADCs available has the tendency to release the active agents en-route to the target, however, this issue has been overcome by the new research.  Marc-André Kasper reported; “The greatest achievement of the new method, however, is that the resulting bond is also stable during blood circulation.”

Further trials were made to test for targeted drug delivery by comparing the new technology with Adcetris, an FDA-approved ADC. The new medication had the same antibody and active ingredients except for a modish phosphoramidite linkage to form a highly effective drug transporter. Upon administration, the innovative medication released significantly fewer active agents over days.

Trials were held on mice which shows that the new technology combats Hodgkin’s lymphoma. The new medication proved to be more effective than the traditional drug compound.

FMP group leader Christian Hackenberger said; “From our results, we conclude that phosphoramidite-linked drug transporters can be administered in lower doses, and that side effects can be further reduced. Thus, the technology has great potential to replace current methods to develop more effective and safer ADCs in the future.”

The researchers are aiming to form ADCs by using phosphonamidates, preclinical studies are already in progress. The company Tubulis awarded the Leibniz Start-Up Prize last year, serves as the platform to conduct further research to market maturity.

Adeena Tariq

Adeena's professional life has been mostly in hospital management, while studying international business in college. Of course, she now covers topics for us in health.

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