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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Health4Life Study Shows Mixed Results for Efficacy of School-Based Intervention in Mental Health

by Manisha Kashyap, PhD

The Health4Life study, a randomized controlled trial (RCT) following CONSORT guidelines and prospectively registered with the Australian and New Zealand Clinical Trials Registry, has yielded mixed results in adolescent mental health outcomes. Ethically approved by multiple institutions, including the University of Sydney, Curtin University, and the University of Queensland, this comprehensive initiative aimed to address prevalent risk behaviors among adolescents across New South Wales (NSW), Queensland (QLD), and Western Australia (WA). This Is a particularly good time to publicize any advances in mental health as May is Mental Health Awareness Month. The report was published on May 23, 2024 in Nature Mental Health by scientists from the Matilda Centre for Research in Mental Health and Substance Use, The University of Sydney, Sydney, NSW, Australia.

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Superfast Science Wins Nobel Prize for Physics–Role of AttoChem

Anne L’Huillier shared 2023 Nobel Prize for Physics with Two Others

In October 2023, the Nobel Prize for Physics was awarded for “experimental methods that generate attosecond pulses of light for studying electron dynamics in matter.” This burgeoning field of research and its practical application have benefitted greatly from the support of a series of European Cooperation in Science & Technology (COST) Actions including the Action Attosecond Chemistry (AttoChem). The 2023 prize was jointly awarded to Pierre Agostini of Ohio State University, Ferenc Krausz of the Max Planck Institute of Quantum Optics in Munich, and Anne L’Huillier of Lund University in Sweden, who is an active member of AttoChem. COST is proud to have worked with all three Prize winners in one or more Actions that have helped build a thriving European research community in this important field.

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Statins Associated with Decreased Risk for Cardiovascular Disease (CVD) and Death, Even in Very Old Adults

A study of adults aged 60 years and older found that the use of statin therapy as primary cardiovascular disease (CVD) prevention was effective for preventing CVD and all-cause mortality, even in adults aged 85 years and older. The study was published in the Annals of Internal Medicine on May 28, 2024. The article is titledBenefits and Risks Associated with Statin Therapy for Primary Prevention in Old and Very Old Adults: Real-World Evidence from a Target Trial Emulation Study.”

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Aging Unraveled: How Our Blood Gets Trickier with Time

by Manisha Kashyap, PhD

Platelets
Ever wonder why as we get older, our bodies seem to throw us more curveballs? Well, researchers from the University of California, Santa Cruz, chiefly, might have just uncovered one of the biggest mysteries yet, and it’s all about our blood. In a study published in Cell on May 14, 2024, lead author Donna M. Poscablo, now a post-doc at Stanford and her colleagues, including senior author E. Camilla Forsberg, PhD, a took a deep dive into the hidden world of aging and its surprising effects on our blood’s clotting ability. The open-access article is titled “An Age-Progressive Platelet Differentiation Path from Hematopoietic Stem Cells Causes Exacerbated Thrombosis.”

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Altering Cellular Interactions Around Amyloid Plaques May Offer Novel Alzheimer’s Treatment Strategies

Innovative research from Mount Sinai also identifies new pathways for research

Researchers at the Icahn School of Medicine at Mount Sinai have made a significant breakthrough in Alzheimer’s disease research by identifying a novel way to potentially slow down or even halt disease progression. The study, which focuses on the role of reactive astrocytes and the plexin-B1 protein in Alzheimer’s pathophysiology, provides crucial insights into brain cell communication and opens the door to innovative treatment strategies. It was published in Nature Neuroscience (DOI 10.1038/s41593-024-01664-w) on May 27. The article is titled “Regulation of Cell Distancing in Peri-Plaque Glial Nets by Plexin-B1 Affects Glial Activation and Amyloid Compaction in Alzheimer’s Disease.”

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Sweet Secrets of the Bayberry: Genetic Insights Set to Transform Fruit Quality

The Chinese bayberry, Myrica rubra, is a subtropical fruit highly valued for its distinctive flavor, nutritional benefits, and economic importance. However, previous genome assemblies lacked sequence continuity, hindering comprehensive genetic studies. Due to these challenges, a detailed investigation of the genetic factors influencing bayberry fruit quality was necessary. Researchers from the State Key Laboratory for Managing Biotic and Chemical Threats to Quality and Safety of Agro-Products have made a monumental discovery. Their work, published (DOI: 10.1093/hr/uhae033) on January 30, 2024, in Horticulture Research, details the assembly of the telomere to telomere (T2T) reference genome for the cultivar “Zaojia” and a genome-wide association study (GWAS) that uncovers the genetic factors influencing bayberry fruit quality.

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Caltech’s Peiwei Chen Shares Harold M. Weintraub Graduate Student Award for Work on “Selfish Genes”

Peiwei Chen, who will receive his PhD in biology from Caltech in June 2024, has been awarded the Harold M. Weintraub Graduate Student Award by the Fred Hutchinson Cancer Research Center. A total of 12 graduate students in the United States and abroad received the honor in 2024. The Weintraub Award honors Harold “Hal” Weintraub, a molecular scientist at the Fred Hutchinson Cancer Center, who passed away in 1995 and was known as an “extraordinary mentor, colleague, collaborator, and friend,” according to the center’s press release.

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New Technique Detects Novel Biomarkers for Kidney Diseases with Nephrotic Syndrome

A groundbreaking study, presented May 25, 2024 at the 61st European Associates (ERA) Congress, has uncovered a significant breakthrough in the diagnosis and monitoring of kidney diseases associated with nephrotic syndrome.1 Using a hybrid technique, researchers identified anti-nephrin autoantibodies as a reliable biomarker for tracking disease progression, opening new avenues for personalized treatment approaches.

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First In-Human Investigator-Initiated Clinical Trial to Launch for Refractory Prostate Cancer Patients: Novel Alpha Therapy Targets Prostate-Specific Membrane Antigen

A research team at Osaka University will start an investigator-initiated clinical trial for refractory prostate cancer patients after successful development of a new alpha-ray therapeutic agent ([At-211] PSMA-5) and confirmation of its efficacy in animal models. This will be a world-first in-human clinical trial with [At-211] PSMA-5.

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