Evidence map›Paper›PMID 40855124›Full record

ArticleNature biomedical engineering2026

Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells.

Tomasz M Grzywa, Alexandra Neeser, Ranjani Ramasubramanian, Anna Romanov, Ryan Tannir, Naveen K Mehta, Benjamin Cossette, Duncan M Morgan, Beatriz Goncalves, Ina Sukaj and 18 more

Abstract read
In one paragraph

Article in Nature biomedical engineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Towards controllable self-amplifying RNA.Nature biomedical engineering · 2026
    Article
  2. Article
  3. Targeted delivery platforms forFrontiers in pharmacology · 2026
    Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors.

Tomasz M GrzywaThe Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1809-248X
Alexandra Neeser *The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Ranjani Ramasubramanian *The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Anna RomanovDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1239-4946
Ryan TannirThe Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0009-3979-7567
Naveen K MehtaDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
Benjamin CossetteDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
Duncan M MorganDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3253-1362
Beatriz GoncalvesThe Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Ina SukajDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
Elisa BergaggioDepartment of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9960-3674
Stephan KadaukeDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2996-8034
Regina M MyersDivision of Oncology, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Luca ParuzzoCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-6505-0194
Guido GhilardiCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Austin CozzoneThe Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Stephen J SchusterDivision of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Noelle FreyDivision of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Libin ZhangDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
Parisa YousefpourDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
Wuhbet AbrahamDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
Heikyung SuhDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
Marco RuellaCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4301-5811
Stephan A GruppDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8030-7595
Roberto ChiarleDepartment of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1564-8531
K Dane WittrupDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2398-5896
Leyuan MaThe Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. Leyuan.ma@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-0583-7470
Darrell J IrvineDavid H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA. djirvine@scripps.edu.ORCID http://orcid.org/0000-0002-8637-1405

Funding

Phenotypic Diversity in COVID-19UL1TR001878 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2016 to 2025
$102.4M
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
Project 3: Combinatorial and gene-editing approaches to enhance the efficacy of CAR T cell therapy of multiple myeloma.P01CA214278 · NCI · UNIVERSITY OF PENNSYLVANIA · PI CARL H. JUNE · 2017 to 2026
$26.8M
Engineering synthetic cellular crosstalk for transplantation toleranceDP2AI164319 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI Leyuan Ma · 2022 to 2026
$2.6M
MODULATION OF CD5 SIGNALING TO ENHANCE ADOPTIVE T-CELL THERAPIES FOR CANCERR37CA262362 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Marco Ruella · 2022 to 2026
$2.6M
Enhancing CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptorR01CA247632 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI IRVINE, DARRELL J · 2020 to 2024
$1.7M
Controlling Vaccine Kinetics with Small Molecule DrugsF32AI164829 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YOUSEFPOUR, PARISA · 2022 to 2024
$184k
Institute for Translational Medicine and Therapeutics (ITMAT) UL1TR001878NCATS NIH HHS UL1 TR001878NCI NIH HHS P01 CA214278NCI NIH HHS P30 CA014051NCI NIH HHS R01 CA247632NCI NIH HHS R37 CA262362NIAID NIH HHS DP2 AI164319NIAID NIH HHS F32 AI164829U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) DP2 AI164319-03
6 · The paper itself

Abstract

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.

Indexed as

Directed Molecular EvolutionReceptors, Chimeric AntigenT-LymphocytesAnimalsAntigens, CD19Cell Line, TumorHumansImmunotherapy, AdoptiveLigandsMicePeptidesPolyethylene GlycolsAntigens, CD19LigandsPeptidesPolyethylene GlycolsReceptors, Chimeric Antigen

Identifiers

PMID40855124
PMCPMC13099375

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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.