Evidence map›Paper›PMID 27323395›Full record

ArticleOncotarget2016

Immunotherapy of acute leukemia by chimeric antigen receptor-modified lymphocytes using an improved Sleeping Beauty transposon platform.

Chiara F Magnani, Nice Turazzi, Fabrizio Benedicenti, Andrea Calabria, Erika Tenderini, Sarah Tettamanti, Greta M P Giordano Attianese, Laurence J N Cooper, Alessandro Aiuti, Eugenio Montini and 2 more

Abstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

  1. Trial
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  15. Article
  16. Review
  17. Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment.International journal of molecular sciences · 2021
    Review
  18. Cellular immunotherapies for cancer.Irish journal of medical science · 2021
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Chiara F MagnaniTettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, San Gerardo Hospital/Fondazione MBBM, Monza, Italy.
Nice TurazziTettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, San Gerardo Hospital/Fondazione MBBM, Monza, Italy.
Fabrizio BenedicentiSan Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
Andrea CalabriaSan Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
Erika TenderiniSan Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
Sarah TettamantiTettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, San Gerardo Hospital/Fondazione MBBM, Monza, Italy.
Greta M P Giordano AttianeseTettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, San Gerardo Hospital/Fondazione MBBM, Monza, Italy.
Laurence J N CooperUniversity of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Alessandro AiutiSan Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
Eugenio MontiniSan Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
Andrea BiondiTettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, San Gerardo Hospital/Fondazione MBBM, Monza, Italy.
Ettore BiagiTettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, San Gerardo Hospital/Fondazione MBBM, Monza, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chimeric antigen receptor (CAR)-modified T-cell adoptive immunotherapy is a remarkable therapeutic option proven effective in the treatment of hematological malignancies. In order to optimize cell manufacturing, we sought to develop a novel clinical-grade protocol to obtain CAR-modified cytokine-induced killer cells (CIKs) using the Sleeping Beauty (SB) transposon system. Administration of irradiated PBMCs overcame cell death of stimulating cells induced by non-viral transfection, enabling robust gene transfer together with efficient T-cell expansion. Upon single stimulation, we reached an average of 60% expression of CD123- and CD19- specific 3rd generation CARs (CD28/OX40/TCRzeta). Furthermore, modified cells displayed persistence of cell subsets with memory phenotype, specific and effective lytic activity against leukemic cell lines and primary blasts, cytokine secretion, and proliferation. Adoptive transfer of CD123.CAR or CD19.CAR lymphocytes led to a significant anti-tumor response against acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) disseminated diseases in NSG mice. Notably, we found no evidence of integration enrichment near cancer genes and transposase expression at the end of the differentiation. Taken all together, our findings describe a novel donor-derived non-viral CAR approach that may widen the repertoire of available methods for T cell-based immunotherapy.

Indexed as

Acute DiseaseAdolescentAnimalsAntigens, CD19Cell Line, TumorChildChild, PreschoolCombined Modality TherapyFemaleGenetic TherapyHumansImmunotherapy, AdoptiveInfantInterleukin-3 Receptor alpha SubunitLeukemiaMiceAntigens, CD19CD19 molecule, humanIL3RA protein, humanInterleukin-3 Receptor alpha SubunitReceptors, Antigen, T-Cellsleeping beauty transposase, humanTransposasesacute lymphoblastic leukemiaacute myelogenous leukemiachimeric antigen receptorcytokine-induced killer cellsSleeping Beauty transposon

Identifiers

PMID27323395
PMCPMC5239498

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.