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Cited by 8Monoclonal and Polyclonal Antibodies ResearchCancer Immunotherapy and Biomarkersvaccines and immunoinformatics approaches

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Simultaneous selection of nanobodies for accessible epitopes on immune cells in the tumor microenvironment

Open access
Sekar, Thillai V., Elghonaimy, Eslam A., Swancutt, Katy L., Diegeler, Sebastian, Gonzalez, Isaac, Hamilton, Cassandra, Leung, Peter Q., Meiler, Jens, Martina, Cristina E., Whitney, Michael, Aguilera, Todd A.·2023·Nature Communications
DOI 10.1038/s41467-023-43038-zPMC PMC10656474

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Abstract

In the rapidly advancing field of synthetic biology, there exists a critical need for technology to discover targeting moieties for therapeutic biologics. Here we present INSPIRE-seq, an approach that utilizes a nanobody library and next-generation sequencing to identify nanobodies selected for complex environments. INSPIRE-seq enables the parallel enrichment of immune cell-binding nanobodies that penetrate the tumor microenvironment. Clone enrichment and specificity vary across immune cell subtypes in the tumor, lymph node, and spleen. INSPIRE-seq identifies a dendritic cell binding clone that binds PHB2. Single-cell RNA sequencing reveals a connection with cDC1s, and immunofluorescence confirms nanobody-PHB2 colocalization along cell membranes. Structural modeling and docking studies assist binding predictions and will guide nanobody selection. In this work, we demonstrate that INSPIRE-seq offers an unbiased approach to examine complex microenvironments and assist in the development of nanobodies, which could serve as active drugs, modified to become drugs, or used as targeting moieties.

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Metadata

Authors
Sekar, T. V., Elghonaimy, E. A., Swancutt, K. L., Diegeler, S., Gonzalez, I., Hamilton, C., Leung, P. Q., Meiler, J., Martina, C. E., Whitney, M., & Aguilera, T. A.
Affiliations
  • Pondicherry University (IN)
  • The University of Texas Southwestern Medical Center (US)
  • Vanderbilt University (US)
  • University of California San Diego (US)
Corresponding author
Aguilera, Todd A.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-11-17
Volume
14
Issue
1
Pages
7473-7473
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-43038-z
PMC
PMC10656474
OpenAlex
W4388750814
Cited by
8
References
3
Citations by year
2026: 4 · 2025: 3 · 2024: 1
FWCI
1.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Cancer Prevention and Research Institute of Texas (RR170051)
  • Mary Kay Foundation
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
tumor microenvironment, immune cells, PHB2, dendritic cells, cDC1, single-cell RNA sequencing, binding prediction
MeSH terms
Epitopes, Tumor Microenvironment, Single-Domain Antibodies

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