Antibody-Peptide Inhibitor Conjugates: A New Path for Cancer Therapy

Elisa Oricchio, PhD
Tumor cells often hijack normal physiological processes to support their growth, exploiting proteins that are in charge of essential cell functions. 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. An example of essential proteins hijacked by cancer cells are the cathepsins, a family of enzymes that is responsible for breaking down other proteins and remodeling the body’s tissues. Cathepsins are implicated in various cancers, osteoporosis, and autoimmune diseases. However, clinical trials with small molecule inhibitors of cathepsins have failed due to either lack of efficacy or toxicity. Now, a team of scientists led by Elisa Oricchio, PhD, and Bruno Correia, PhD, at EPFL (École Polytechnique Fédérale de Lausanne) has developed a novel approach to overcome these limitations. They created a modular drug platform that conjugates non-natural peptide inhibitors (NNPIs) with antibodies, creating antibody-peptide inhibitor conjugates (APICs). This method ensures that the inhibitors are delivered specifically to cancer cells, thereby reducing systemic side effects and increasing therapeutic efficacy. The work was reported on May 29, 2024 in Nature Chemical Biology. The article is titled “Antibody–Peptide Conjugates Deliver Covalent Inhibitors Blocking Oncogenic Cathepsins.”
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