Evidence map›Paper›PMID 31178392›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019

Effect of Cryopreservation on Autologous Chimeric Antigen Receptor T Cell Characteristics.

Sandhya R Panch, Sandeep K Srivastava, Nasha Elavia, Andrew McManus, Shutong Liu, Ping Jin, Steven L Highfill, Xiaobai Li, Pradeep Dagur, James N Kochenderfer and 5 more

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
–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

58 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  8. Review
  9. High-dimensional temporal mapping of CAR T cells reveals phenotypic and functional remodeling during manufacturing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  10. Review
  11. Current Role of CAR-T Therapy in Haematological Care.Advances in experimental medicine and biology · 2025
    Review
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  13. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Sandhya R PanchCenter for Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA. Electronic address: sandhya.panch@nih.gov.
Sandeep K SrivastavaCenter for Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
Nasha ElaviaCenter for Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
Andrew McManusCenter for Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
Shutong LiuCenter for Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
Ping JinCenter for Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
Steven L HighfillCenter for Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
Xiaobai LiBiostatistics and Clinical Epidemiology Service, NIH Clinical Center, Bethesda, MD, USA.
Pradeep DagurNational Heart Lung and Blood Institute, NIH, Bethesda, MD, USA.
James N KochenderferNational Cancer Institute, NIH, Bethesda, MD, USA.
Terry J FryPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Crystal L MackallCancer Immunology and Immunotherapy Program, Stanford University, Stanford, CA, USA.
Daniel LeeDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA.
Nirali N ShahPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
David F StroncekCenter for Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.

Funding

New Chimeric Antigen Receptors for Treating Hematologic MalignanciesZIABC011417 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KOCHENDERFER, JAMES · 2011 to 2025
$8.3M
Develop novel assays for assessing cellular and gene therapiesZIACL002119 · CLC · CLINICAL CENTER · PI STRONCEK, DAVID · 2010 to 2025
$0k
Development of novel cell and gene therapiesZIACL002120 · CLC · CLINICAL CENTER · PI STRONCEK, DAVID · 2009 to 2025
$0k
6 · The paper itself

Abstract

As clinical applications for chimeric antigen receptor T cell (CART) therapy extend beyond early phase trials, commercial manufacture incorporating cryopreservation steps becomes a logistical necessity. The effect of cryopreservation on CART characteristics is unclear. We retrospectively evaluated the effect of cryopreservation on product release criteria and in vivo characteristics in 158 autologous CART products from 6 single-center clinical trials. Further, from 3 healthy donor manufacturing runs, we prospectively identified differentially expressed cell surface markers and gene signatures among fresh versus cryopreserved CARTs. Within 2 days of culture initiation, cell viability of the starting fraction (peripheral blood mononuclear cells [PBMNCs]) decreased significantly in the cryo-thawed arm compared to the fresh arm. Despite this, PBMNC cryopreservation did not affect final CART fold expansion, transduction efficiency, CD3%, or CD4:CD8 ratios. In vivo CART persistence and clinical responses did not differ among fresh and cryopreserved final products. In healthy donors, compared to fresh CARTs, early apoptotic cell-surface markers were significantly elevated in cryo-thawed CARTs. Cryo-thawed CARTs also demonstrated significantly elevated expression of mitochondrial dysfunction, apoptosis signaling, and cell cycle damage pathways. Cryopreservation during CART manufacture is a viable strategy, based on standard product release parameters. The clinical impact of cryopreservation-related subtle micro-cellular damage needs further study.

Indexed as

AdolescentAdultAgedApoptosisAutoantigensCD4-CD8 RatioCell CycleCell SurvivalChildCryopreservationFemaleHumansImmunotherapy, AdoptiveMaleMiddle AgedNeoplasmsAutoantigensReceptors, Chimeric AntigenCAR T cellschimeric antigen receptor T cellscryopreservationearly apoptotic cellsgene expression profilingleukemialymphomamultiple myelomaPBMNCviability

Identifiers

PMID31178392
PMCPMC6612799

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.