ArticlemAbs2015
Stability engineering of anti-EGFR scFv antibodies by rational design of a lambda-to-kappa swap of the VL framework using a structure-guided approach.
Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed.
- Single-Chain Variable Fragment Fusion Proteins for Targeted Delivery and Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Recombinant single-chain variable fragment-based immunoassay for the authentication of Vietnamese ginseng via quantitative detection of majonoside R2.Journal of ginseng research · 2026Article
- scFv-based biologics in diabetes: from therapeutic potential to clinical prospects.Frontiers in immunology · 2026Review
- Impact of Light-Chain Variants on the Expression of Therapeutic Monoclonal Antibodies in HEK293 and CHO Cells.Antibodies (Basel, Switzerland) · 2025Article
- Contextualising the developability risk of antibodies with lambda light chains using enhanced therapeutic antibody profiling.Communications biology · 2024Article
- Chemokine Receptors CCR6 and PD1 Blocking scFv E27 Enhances Anti-EGFR CAR-T Therapeutic Efficacy in a Preclinical Model of Human Non-Small Cell Lung Carcinoma.International journal of molecular sciences · 2023Article
- How can we discover developable antibody-based biotherapeutics?Frontiers in molecular biosciences · 2023Review
- Engineered fast-dissociating antibody fragments for multiplexed super-resolution microscopy.Cell reports methods · 2022Article
- Article
- Modeling Immunity with Rosetta: Methods for Antibody and Antigen Design.Biochemistry · 2021Review
- T cell circuits that sense antigen density with an ultrasensitive threshold.Science (New York, N.Y.) · 2021Article
- Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020Review
- Antibody Structure and Function: The Basis for Engineering Therapeutics.Antibodies (Basel, Switzerland) · 2019Review
- Expanding the Boundaries of Biotherapeutics with Bispecific Antibodies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018Review
- Production of a germline-humanized cetuximab scFv and evaluation of its activity in recognizing EGFR- overexpressing cancer cells.Human vaccines & immunotherapeutics · 2018Article
- RosettaAntibodyDesign (RAbD): A general framework for computational antibody design.PLoS computational biology · 2018Article
- The impact of structural biology in medicine illustrated with four case studies.Journal of molecular medicine (Berlin, Germany) · 2018Review
- Decomposing Dynamical Couplings in Mutated scFv Antibody Fragments into Stabilizing and Destabilizing Effects.Journal of the American Chemical Society · 2017Article
- Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics.Frontiers in immunology · 2017Review
- Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Phage-display technology facilitates rapid selection of antigen-specific single-chain variable fragment (scFv) antibodies from large recombinant libraries. ScFv antibodies, composed of a VH and VL domain, are readily engineered into multimeric formats for the development of diagnostics and targeted therapies. However, the recombinant nature of the selection strategy can result in VH and VL domains with sub-optimal biophysical properties, such as reduced thermodynamic stability and enhanced aggregation propensity, which lead to poor production and limited application. We found that the C10 anti-epidermal growth factor receptor (EGFR) scFv, and its affinity mutant, P2224, exhibit weak production from E. coli. Interestingly, these scFv contain a fusion of lambda3 and lambda1 V-region (LV3 and LV1) genes, most likely the result of a PCR aberration during library construction. To enhance the biophysical properties of these scFvs, we utilized a structure-based approach to replace and redesign the pre-existing framework of the VL domain to one that best pairs with the existing VH. We describe a method to exchange lambda sequences with a more stable kappa3 framework (KV3) within the VL domain that incorporates the original lambda DE-loop. The resulting scFvs, C10KV3_LV1DE and P2224KV3_LV1DE, are more thermodynamically stable and easier to produce from bacterial culture. Additionally, C10KV3_LV1DE and P2224KV3_LV1DE retain binding affinity to EGFR, suggesting that such a dramatic framework swap does not significantly affect scFv binding. We provide here a novel strategy for redesigning the light chain of problematic scFvs to enhance their stability and therapeutic applicability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.