Evidence map›Paper›PMID 34135100›Full record

ArticleJournal for immunotherapy of cancer2021

Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts.

Concetta Quintarelli, Marika Guercio, Simona Manni, Iolanda Boffa, Matilde Sinibaldi, Stefano Di Cecca, Simona Caruso, Zeinab Abbaszadeh, Antonio Camera, Biancamaria Cembrola and 18 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 23% of its field
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

9 citing papers in PubMed, 11 citations in OpenAlex.

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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

28 authors at 5 institutions in 4 countries.

Concetta QuintarelliDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy concetta.quintarelli@opbg.net.ORCID 0000-0002-4343-9705
Marika GuercioDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Simona ManniDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Iolanda BoffaDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Matilde SinibaldiDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Stefano Di CeccaDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Simona CarusoDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Zeinab AbbaszadehDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Antonio CameraDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Biancamaria CembrolaDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Roselia CicconeDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Alberto OrfaoTranslational Program, Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL), CIBERONC and Department of Medicine and Cytometry Service (NUCLEUS Research Support Platform), University of Salamanca (USAL), Salamanca, Spain.
Lourdes Martin-MartinTranslational Program, Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL), CIBERONC and Department of Medicine and Cytometry Service (NUCLEUS Research Support Platform), University of Salamanca (USAL), Salamanca, Spain.
Sara Gutierrez-HerreroTranslational Program, Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL), CIBERONC and Department of Medicine and Cytometry Service (NUCLEUS Research Support Platform), University of Salamanca (USAL), Salamanca, Spain.
Maria Herrero-GarciaTranslational Program, Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL), CIBERONC and Department of Medicine and Cytometry Service (NUCLEUS Research Support Platform), University of Salamanca (USAL), Salamanca, Spain.
Gianni CazzanigaCentro Ricerca Tettamanti, Pediatric Department, Fondazione MBBM, University of Milan-Bicocca, Monza, Italy.ORCID 0000-0003-2955-4528
Vittorio NunesCentro Ricerca Tettamanti, Pediatric Department, Fondazione MBBM, University of Milan-Bicocca, Monza, Italy.
Simona SongiaCentro Ricerca Tettamanti, Pediatric Department, Fondazione MBBM, University of Milan-Bicocca, Monza, Italy.
Paolo MarcatiliDepartment of Bio and Health Informatics, Technical University of Denmark, Kgs. Lyngby, Denmark.
Frederikke I MarinDepartment of Bio and Health Informatics, Technical University of Denmark, Kgs. Lyngby, Denmark.
Marco RuellaDepartment of Pathology and Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0003-4301-5811
Valentina BertainaDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Luciana VintiDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Francesca Del BufaloDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.ORCID 0000-0001-9643-3465
Mattia AlgeriDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Pietro MerliDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Biagio De AngelisDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Franco LocatelliDepartment Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Bambino Gesù Children's Hospital · ITUniversidad de Salamanca · ESUniversity of Milano-Bicocca · ITTechnical University of Denmark · DKUniversity of Pennsylvania · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3M
Resistance To Targeted Immunotherapies:CART19 as a ParadigmR00CA212302 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RUELLA, MARCO · 2018 to 2020
$608k
Resistance To Targeted Immunotherapies:CART19 as a ParadigmK99CA212302 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RUELLA, MARCO · 2017 to 2018
$348k
NCI NIH HHS K99 CA212302NCI NIH HHS P30 CA016520NCI NIH HHS R00 CA212302
6 · The paper itself

Abstract

Chimeric antigen receptor T-cells (CAR T-cells) for the treatment of relapsing/refractory B-cell precursor acute lymphoblastic leukemia have led to exciting clinical results. However, CAR T-cell approaches revealed a potential risk of CD19-/CAR+ leukemic relapse due to inadvertent transduction of leukemia cells.

background

methodsWe evaluated the impact of a high percentage of leukemia blast contamination in patient-derived starting material (SM) on CAR T-cell drug product (DP) manufacturing.

resultsThe presence of large amounts of CD19+ cells in SM did not affect the transduction level of DPs, as well as the CAR T-cell rate of expansion at the end of standard production of 14 days. DPs were deeply characterized by flow cytometry and molecular biology for Ig-rearrangements, showing that the level of B-cell contamination in DPs did not correlate with the percentage of CD19+ cells in SM, in the studied patient cohort. Moreover, we investigated whether CAR design may affect the control of CAR+ leukemia cells. We provided evidences that CAR.CD19 short linker (SL) prevents complete epitope masking in CD19+CAR+ leukemia cells and we demonstrated

conclusionsTaken together, these data suggest that a VL-VH SL may result in a safe CAR-T product, even when manufacturing starts from biological materials characterized by heavy contamination of leukemia blasts.

Indexed as

AnimalsCell Line, TumorDisease Models, AnimalEpitopesHumansLeukemia, B-CellMiceReceptors, Chimeric AntigenEpitopesReceptors, Chimeric Antigenadoptivecell engineeringchimeric antigenhematologic neoplasmsimmunotherapyreceptorstranslational medical research

Identifiers

PMID34135100
PMCPMC8211055
OpenAlexW3166061664

What OpenQuestion holds

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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.