Extensive crosstalk among ErbB/HER receptors suggests that blocking signaling from more than one family member may be essential to effectively treat cancer and limit drug resistance. We generated a conventional IgG molecule MEHD7945A with dual HER3/EGFR specificity by phage display engineering and used structural and mutational studies to understand how a single antigen recognition surface binds two epitopes with high affinity. As a human IgG1, MEHD7945A exhibited dual action by inhibiting EGFR- and HER3-mediated signaling in vitro and in vivo and the ability to engage immune effector functions. Compared with monospecific anti-HER antibodies, MEHD7945A was more broadly efficacious in multiple tumor models, showing that combined inhibition of EGFR and HER3 with a single antibody is beneficial.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ccr.2011.09.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Aquaculture source of atmospheric NO in China: Comparison of system types, management practices and measurement methods.
Environ Res
December 2024
School of Environmental Ecology and Biological Engineering, Institute of Changjiang Water Environment and Ecological Security, Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, Wuhan Institute of Technology, Wuhan, 430205, China. Electronic address:
Aquaculture systems contribute to atmospheric NO, but the magnitude of this NO source is largely uncertain. Here, we synthesized data from 139 aquaculture sites based on 59 peer-reviewed publications, and estimated that China's aquaculture systems emitted 9.68 Gg N yr (4.
View Article and Find Full Text PDFA brain-penetrant bispecific antibody lowers oligomeric alpha-synuclein and activates microglia in a mouse model of alpha-synuclein pathology.
Neurotherapeutics
December 2024
Department of Public Health and Caring Sciences, Uppsala University, 751 85, Uppsala, Sweden. Electronic address:
Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, linked to aggregation of alpha-synuclein (αSYN) into Lewy bodies. Current treatments are symptomatic and do not halt or reverse the neurodegeneration. Immunotherapy targeting aggregated αSYN shows potential, but therapeutic efficacy is limited by poor brain penetration of antibodies.
View Article and Find Full Text PDFFacilitating high throughput bispecific antibody production and potential applications within biopharmaceutical discovery workflows.
MAbs
December 2024
Large Molecule Discovery, GSK, GSK Medicines Research Centre, Stevenage, UK.
A major driver for the recent investment surge in bispecific antibody (bsAb) platforms and products is the multitude of distinct mechanisms of action that bsAbs offer compared to a combination of two monoclonal antibodies. Four bsAb products were granted first regulatory approvals in the US or EU during 2023 and the biopharmaceutical industry pipeline is brimming with bsAb candidates across a broad range of therapeutic applications. In previously reported bsAb discovery campaigns, following a hypothesis-based choice of two specific target proteins, selections and screening activities have often been performed in mono-specific formats.
View Article and Find Full Text PDFCan Thinning Foster Forest Genetic Adaptation to Drought? A Demo-Genetic Modelling Approach With Disturbance Regimes.
Evol Appl
December 2024
INRAE, UR 629 Ecologie des Forêts Méditerranéennes (URFM), Domaine Saint Paul-Site Agroparc Avignon France.
Article Synopsis
- The study examines how management practices in forests can affect natural selection and adaptations to environmental stress, specifically drought.
- By using a modeling approach with the Luberon2 simulation, researchers explored the effects of tree thinning on growth traits and drought sensitivity over three generations.
- Results indicate that while thinning reduced competition pressures, traditional practices that favor larger trees may unintentionally enhance genetic traits that are not beneficial for long-term drought resilience.
A genus-wide study on venom proteome variation and phospholipase A inhibition in Asian lance-headed pit vipers (genus: Trimeresurus).
Comp Biochem Physiol C Toxicol Pharmacol
February 2025
Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; School of Medicine, College of Life Sciences and Medicine, National Tsing Hua University, Hsinchu, Taiwan; Institute of Bioinformatics and Structural Biology, College of Life Sciences and Medicine, National Tsing Hua University, Hsinchu, Taiwan. Electronic address:
Article Synopsis
- The research utilized techniques like SDS-PAGE and LCMS/MS to investigate venom protein variability and identified conserved protein families with diverse expressions that do not follow snake evolutionary lineages.
- Key findings indicate that while certain enzymes' expression correlates weakly with venom effects, phospholipase A activity strongly correlates with its abundance, and a small molecule inhibitor, varespladib, may effectively inhibit PLA activities, suggesting its potential as a therapeutic for snakebite treatment.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!