Tumor cells often hijack normal physiological processes to support their growth, exploiting proteins that are in charge of essential cell functions.
May 29 2024Ecole Polytechnique Federale de Lausanne It is therefore important to block the activity of these proteins only in cancer cells without affecting their crucial roles in healthy tissues. For this reason, classical approaches using small molecules that induce systemic inhibition across all cells in the body can lead to severe side effects.
Now, a team of scientists led by Elisa Oricchio and Bruno Correia at EPFL has developed a novel approach to overcome these limitations. They created a modular drug platform that conjugates non-natural peptide inhibitors with antibodies, creating antibody-peptide inhibitor conjugates . This method ensures that the inhibitors are delivered specifically to cancer cells, thereby reducing systemic side effects and increasing therapeutic efficacy.
The researchers began by designing NNPIs that covalently bind to and inhibit cathepsins. They modified peptide sequences to include a Michael acceptor, a chemical moiety that makes it easier to form a stable bond with cathepsins. The researchers identified several strong inhibitors against four different cathepsins, namely cathepsin S, B, K and L. By attaching these inhibitors to antibodies that recognize CD22, CD79, HER2, and Siglec15, the researchers could precisely deliver the NNPIs to lymphoma cells, breast cancer cells and osteoclasts. This leverages the natural ability of antibodies to be internalized by target cells, precisely directing the inhibitors where they are needed.
Cancer Cancer Therapy Antibodies Breast Cancer Cell Efficacy ELISA Lymphoma Osteoporosis Protein Research Small Molecules Tumor
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