Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells Article Swipe
Tomasz M. Grzywa
,
Alexandra Neeser
,
Ranjani Ramasubramanian
,
Anna Romanov
,
Ryan Tannir
,
Naveen K. Mehta
,
Benjamin Cossette
,
Duncan M. Morgan
,
Beatriz Gonçalves
,
Ina Sukaj
,
Elisa Bergaggio
,
Stephan Kadauke
,
Regina M. Myers
,
Luca Paruzzo
,
Guido Ghilardi
,
Aj Cozzone
,
Stephen J. Schuster
,
Norbert Frey
,
Libin Zhang
,
Parisa Yousefpour
,
Wuhbet Abraham
,
Heikyung Suh
,
Marco Ruella
,
Stephan A. Grupp
,
Roberto Chiarle
,
K. Dane Wittrup
,
Leyuan Ma
,
Darrell J. Irvine
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41551-025-01470-0
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41551-025-01470-0
Chimeric antigen receptor (CAR) T cell therapy targeting CD19 elicits remarkable clinical efficacy in B cell malignancies, but many patients relapse owing to failed expansion and/or progressive loss of CAR-T cells. We recently reported a strategy to potently restimulate CAR-T cells in vivo, enhancing their functionality by administration of a vaccine-like stimulus comprised of surrogate peptide ligands for a CAR linked to a lymph node-targeting amphiphilic PEG-lipid (amph-vax). Here we demonstrate a general strategy to discover and optimize peptide mimotopes enabling amph-vax generation for any CAR. We use yeast surface display to identify peptide binders to FMC63 (the scFv used in clinical CD19 CARs), which are then subsequently affinity matured by directed evolution. CAR-T vaccines using these optimized mimotopes triggered marked expansion and memory development of CD19 CAR-T cells in both syngeneic and humanized mouse models of B-acute lymphoblastic leukaemia/lymphoma, and enhanced control of disease progression compared with CD19 CAR-T-only-treated mice. This approach enables amph-vax boosting to be applied to any clinically relevant CAR-T cell product.
Related Topics
Concepts
Chimeric antigen receptor
CD19
Cancer research
In vivo
Antigen
T cell
Immunology
Biology
Medicine
Chemistry
Immune system
Biotechnology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41551-025-01470-0
- https://www.nature.com/articles/s41551-025-01470-0.pdf
- OA Status
- hybrid
- References
- 75
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4413494869
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4413494869Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s41551-025-01470-0Digital Object Identifier
- Title
-
Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cellsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-08-25Full publication date if available
- Authors
-
Tomasz M. Grzywa, Alexandra Neeser, Ranjani Ramasubramanian, Anna Romanov, Ryan Tannir, Naveen K. Mehta, Benjamin Cossette, Duncan M. Morgan, Beatriz Gonçalves, Ina Sukaj, Elisa Bergaggio, Stephan Kadauke, Regina M. Myers, Luca Paruzzo, Guido Ghilardi, Aj Cozzone, Stephen J. Schuster, Norbert Frey, Libin Zhang, Parisa Yousefpour, Wuhbet Abraham, Heikyung Suh, Marco Ruella, Stephan A. Grupp, Roberto Chiarle, K. Dane Wittrup, Leyuan Ma, Darrell J. IrvineList of authors in order
- Landing page
-
https://doi.org/10.1038/s41551-025-01470-0Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41551-025-01470-0.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://www.nature.com/articles/s41551-025-01470-0.pdfDirect OA link when available
- Concepts
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Chimeric antigen receptor, CD19, Cancer research, In vivo, Antigen, T cell, Immunology, Biology, Medicine, Chemistry, Immune system, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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75Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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