ArticlemAbs
Rare, high-affinity mouse anti-PD-1 antibodies that function in checkpoint blockade, discovered using microfluidics and molecular genomics.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- Anti-PD-1 single-chain variable fragments in cancer immunotherapy: from molecular engineering to clinical translation.Cancer chemotherapy and pharmacology · 2026Review
- A droplet microfluidics-based platform for generating target-specific, natively-paired immune libraries and identifying potent and developable antibodies.Scientific reports · 2026Article
- Review
- Article
- A Targeted Integration-Based CHO Cell Platform for Simultaneous Antibody Display and Secretion.Antibodies (Basel, Switzerland) · 2025Article
- Article
- High-throughput specificity profiling of antibody libraries using ribosome display and microfluidics.Cell reports methods · 2024Article
- PPB-Affinity: Protein-Protein Binding Affinity dataset for AI-based protein drug discovery.Scientific data · 2024Article
- Fluorescence-activated droplet sequencing (FAD-seq) directly provides sequences of screening hits in antibody discovery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Sequencing the B Cell Receptor Repertoires of Antibody-Deficient Individuals With and Without Infection Susceptibility.Journal of clinical immunology · 2023Article
- Article
- Toripalimab-associated diabetes mellitus: a case report from the community of Southern China.Endocrinology, diabetes & metabolism case reports · 2023Article
- Application of recombinant antibodies for treatment ofFrontiers in immunology · 2022Review
- Directed Evolution in Drops: Molecular Aspects and Applications.ACS synthetic biology · 2021Review
- The future of microfluidics in immune checkpoint blockade.Cancer gene therapy · 2021Review
- Characterization of a single chain variable fragment of nivolumab that targets PD-1 and blocks PD-L1 binding.Protein expression and purification · 2021Article
- Antigen discovery tools for adaptive immune receptor repertoire research.Current opinion in systems biology · 2020Article
- Exhaustive Search of the Receptor Ligands by the CyCLOPS (Cytometry Cell-Labeling Operable Phage Screening) Technique.International journal of molecular sciences · 2020Article
- Rapid isolation of antigen-specific B-cells using droplet microfluidics.RSC advances · 2020Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Conventionally, mouse hybridomas or well-plate screening are used to identify therapeutic monoclonal antibody candidates. In this study, we present an alternative to hybridoma-based discovery that combines microfluidics, yeast single-chain variable fragment (scFv) display, and deep sequencing to rapidly interrogate and screen mouse antibody repertoires. We used our approach on six wild-type mice to identify 269 molecules that bind to programmed cell death protein 1 (PD-1), which were present at an average of 1 in 2,000 in the pre-sort scFv libraries. Two rounds of fluorescence-activated cell sorting (FACS) produced populations of PD-1-binding scFv with a mean enrichment of 800-fold, whereas most scFv present in the pre-sort mouse repertoires were de-enriched. Therefore, our work suggests that most of the antibodies present in the repertoires of immunized mice are not strong binders to PD-1. We observed clusters of related antibody sequences in each mouse following FACS, suggesting evolution of clonal lineages. In the pre-sort repertoires, these putative clonal lineages varied in both the complementary-determining region (CDR)3K and CDR3H, while the FACS-selected PD-1-binding subsets varied primarily in the CDR3H. PD-1 binders were generally not highly diverged from germline, showing 98% identity on average with germline V-genes. Some CDR3 sequences were discovered in more than one animal, even across different mouse strains, suggesting convergent evolution. We synthesized 17 of the anti-PD-1 binders as full-length monoclonal antibodies. All 17 full-length antibodies bound recombinant PD-1 with K
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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.