Rational design of a common-light-chain bispecific antibody unlocks broad antitumor activity
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For patients with EGFR-mutant non-small cell lung cancer, resistance to tyrosine kinase inhibitors (TKIs)—most often driven by MET amplification—remains a major clinical obstacle. Researchers have now developed a structure-guided rational design method that converts existing monoclonal antibodies into common-light-chain bispecific antibodies, without large-scale library screening. Applying this framework, the team generated ALK101, an EGFR×c-MET bispecific antibody with binding affinity and biological activity comparable to the approved benchmark amivantamab. ALK101 showed robust antitumor efficacy across multiple tumor models, including tumors resistant to first-, second-, and third-generation TKIs, together with favorable pharmacokinetic and safety profiles in non-human primates. The study establishes a generalizable route to accelerate bispecific antibody development and nominates ALK101 as a promising clinical candidate.
Diabetic kidney disease (DKD) is commonly associated with metabolic disorders and inflammatory injury, but gut-resident bacteria may also contribute to renal damage. Researchers found that Escherichia coli/Escherichia-Shigella was enriched in the gut microbiota of patients and mice with DKD. In diabetic mice, viable enteroaggregative Escherichia coli (EAEC) crossed the impaired intestinal barrier and colonized the kidneys. Oral administration of mouse- or patient-derived EAEC increased renal bacterial burden, inflammation, and fibrosis. The researchers subsequently isolated an EAEC-specific bacteriophage, EAWsc9, that selectively lysed EAEC and carried no known virulence or antimicrobial resistance genes. After three weeks of oral treatment with EAWsc9, db/db mice showed reductions in renal EAEC burden, serum creatinine, blood urea nitrogen, indoxyl sulfate, inflammatory markers, and fibrosis. These findings extend the gut–kidney axis beyond microbial metabolites to include the translocation of viable bacteria and suggest a precision, microbiota-directed antibacterial strategy for addressing infection-associated renal injury in DKD.
Skin is an entry point for tick-borne pathogens, but the responses of its different cell types remain incompletely understood. Researchers reporting in hLife mapped skin-cell responses to Rickettsia heilongjiangensis in wild-type mice, mice lacking type I or both type I and type II interferon receptors. They also examined patient samples and clinical data. Macrophage gene expression varied across interferon receptor backgrounds, whereas neutrophils retained signatures related to oxidative phosphorylation and protein degradation across all three mouse models. Fibroblast responses also differed in timing. In evaluable human tick-bite skin samples, the lipid peroxidation marker MDA appeared only in lesions from rickettsial PCR-positive patients, while MPO and OGG1 staining occurred in both PCR-positive and PCR-negative patients. Among patients with confirmed spotted fever group rickettsial infection and clear lesion and fever information, fever was less frequent in those with local skin lesions. The findings identify distinct cellular responses and a clinical association, while leaving open whether these local responses influence infection outcomes.
A growing surplus of refinery sulfur could find a new use in asphalt production, reducing reliance on petroleum-based bitumen and lowering costs. But a new academic review highlights unanswered questions about emissions, human exposure and long-term health implications, calling for safer formulations and life-cycle assessment of sulfur-modified asphalt.
Researchers from Wuhan University have developed a new Uncertainty-Aware Filtering (UAF) algorithm that significantly enhances spacecraft autonomous navigation in deep-space environments characterized by weak gravity, strong perturbations, and limited prior knowledge, which is published in the Chinese Journal of Aeronautics (https://doi.org/10.1016/j.cja.2025.103971). The method shows clear advantages over conventional Extended Kalman Filter (EKF) and Unscented Kalman Filter (UKF) approaches and has been validated using simulations of China’s Tianwen-2 mission to asteroid 311P/PANSTARRS.