Science TLDR

https://doi.org/10.1007/s11186-025-09635-1

https://doi.org/10.1038/s41598-025-03665-6

https://www.jstor.org/stable/2183914

Mixing it up a little with an episode covering 3 papers on the same topic. Antibody tumor penetration: Transport opposed by systemic and antigen-mediated clearancedoi:10.1016/j.addr.2008.04.012. A highly stable human single-domain antibody-drug conjugate exhibits superior penetration and treatment of solid tumorshttps://doi.org/10.1016/j.ymthe.2022.04.013. Influence of molecular size on tissue dis...

https://doi.org/10.1038/s41562-025-02196-4

doi: 10.1038/s41586-025-09053-4

https://doi.org/10.1038/s41586-025-08997-x

https://doi.org/10.1038/s41587-025-02654-4

DOI: 10.1056/NEJMoa2504747

https://www.nature.com/articles/s41586-025-08888-1

https://doi.org/10.1038/s41586-025-08852-z

DOI: 10.1038/s41586-025-08800-x

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003052

https://www.nature.com/articles/s42256-025-01005-x

https://www.biorxiv.org/content/10.1101/2025.02.19.639056v1

DOI: 10.1158/2643-3230.BCD-23-0258

DOI: 10.1038/s41467-025-56572-9 Key Points: - Introduces AlphaFold-Metainference, a new method combining AlphaFold predictions with physics simulations - Notable because AlphaFold was trained on structured proteins but shows surprising accuracy with disordered ones - Validated against experimental data from 11 different disordered proteins using SAXS (small-angle X-ray scattering) - Further valida...

DOI: 10.1038/s41590-023-01687-8 Key Points: - Research focuses on using engineered macrophages (CAR-iMACs) instead of typical CAR T cells to fight solid tumors - Started with iPSCs (induced pluripotent stem cells) which were differentiated into macrophages and engineered with CARs - Created two versions: - First generation with CD3ζ domain - Second generation with added TIR domain - Second generat...

DOI: 10.1056/NEJMoa2410965 Key Points: - Phase 3 trial testing obinutuzumab (anti-CD20 monoclonal antibody) + standard therapy vs placebo + standard therapy for lupus nephritis - Primary endpoint: Complete renal response at week 76 - Notable finding: 46.4% response with obinutuzumab vs 33.1% with placebo (13.4% improvement, p=0.02) Trial Design: - 271 adult patients with active lupus nephritis - R...

DOI: 10.1126/scitranslmed.adl6432 Key Points: The Research Problem: CAR-T cell therapy has been successful for blood cancers but faces challenges with solid tumors Major challenge: "On-target, off-tumor toxicity" where CAR-T cells attack healthy tissues Previous patient death case: HER2-targeted CAR-T cells attacked lung tissue due to HER2 expression on lung cells Study Focus: Target: EpCAM (epith...

DOI: 10.1038/s42256-024-00971-y Key Topics: - New deep learning model MUNIS for predicting CD8+ T-cell epitopes - Implications for vaccine development and personalized medicine - Real-world validation using Epstein-Barr virus (EBV) Background Science: - HLAI molecules display protein fragments (epitopes) on cell surfaces - CD8+ T-cells recognize foreign epitopes to trigger immune response - Tradit...

DOI: https://doi.org/10.1186/s40035-025-00465-w Key Discussion Points: 1. Overview of Current Landscape - Three FDA-approved second-generation antibodies: Aducanumab, Lecanemab, Donanemab - Lecanemab recently received traditional FDA approval - Represents validation of amyloid cascade hypothesis 2. Individual Antibody Profiles: Aducanumab - Derived from memory B cells of both healthy and cognitive...

DOI: 10.1126/science.adn9390 Key points: The Itch-Scratch Paradox Scratching is an evolutionarily conserved behavior but seems counterproductive as it worsens inflammation Research found scratching serves both harmful and beneficial purposes: Can exacerbate allergic skin conditions Helps protect against bacterial infections like S. aureus Provides insight into why scratching is pleasurable despite...

DOI: 10.1126/scitranslmed.adq1086 Central Idea: This study examines how previous COVID-19 vaccination influences both innate and adaptive immune responses during breakthrough infections. The researchers found that vaccination helps prevent excessive activation of the immune system, particularly in innate immune cells like monocytes and natural killer (NK) cells. Key Concepts: Breakthrough vs Prima...

DOI: https://doi.org/10.1038/s41467-024-55399-0 Central Idea: This paper presents an ML-guided platform for accelerating enzyme engineering by combining cell-free protein synthesis, functional screening, and machine learning to rapidly optimize enzymes for multiple distinct chemical reactions. The approach is demonstrated by engineering variants of an amide synthetase (McbA) to improve synthesis o...