Evidence map›Paper›PMID 32788237›Full record

ArticleJournal for immunotherapy of cancer2020

Efficient elimination of primary B-ALL cells in vitro and in vivo using a novel 4-1BB-based CAR targeting a membrane-distal CD22 epitope.

Talia Velasco-Hernandez, Samanta Romina Zanetti, Heleia Roca-Ho, Francisco Gutierrez-Aguera, Paolo Petazzi, Diego Sánchez-Martínez, Oscar Molina, Matteo Libero Baroni, Jose Luis Fuster, Paola Ballerini and 4 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 21% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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  7. Review
  8. Targeting CD22 for B-cell hematologic malignancies.Experimental hematology & oncology · 2023
    Review
  9. Article
  10. Article
  11. A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  12. Review
  13. Article
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

14 authors at 7 institutions in 2 countries.

Talia Velasco-HernandezJosep Carreras Leukemia Research Institute, Barcelona, Spain tvelasco@carrerasresearch.org pmenendez@carrerasresearch.org.ORCID 0000-0003-2183-7443
Samanta Romina ZanettiJosep Carreras Leukemia Research Institute, Barcelona, Spain.ORCID 0000-0002-9052-8751
Heleia Roca-HoJosep Carreras Leukemia Research Institute, Barcelona, Spain.
Francisco Gutierrez-AgueraJosep Carreras Leukemia Research Institute, Barcelona, Spain.
Paolo PetazziJosep Carreras Leukemia Research Institute, Barcelona, Spain.
Diego Sánchez-MartínezJosep Carreras Leukemia Research Institute, Barcelona, Spain.
Oscar MolinaJosep Carreras Leukemia Research Institute, Barcelona, Spain.
Matteo Libero BaroniJosep Carreras Leukemia Research Institute, Barcelona, Spain.
Jose Luis FusterSección de Oncohematología Pediátrica, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biosanitaria (IMIB), El Palmar, Murcia, Spain.
Paola BalleriniDepartment of Pediatric Hemato-oncology, Armand-Trousseau Childrens Hospital, Paris, Île-de-France, France.
Clara BuenoJosep Carreras Leukemia Research Institute, Barcelona, Spain.
Narcis Fernandez-FuentesDepartment of Biosciences, Universitat de Vic - Universitat Central de Catalunya, Vic, Catalunya, Spain.
Pablo EngelInstitut d'Investigacions Biomèdiques, August Pi i Sunyer, Barcelona, Spain.ORCID 0000-0001-8410-252X
Pablo MenendezJosep Carreras Leukemia Research Institute, Barcelona, Spain tvelasco@carrerasresearch.org pmenendez@carrerasresearch.org.
Josep Carreras Leukaemia Research Institute · ESConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESInstitució Catalana de Recerca i Estudis Avançats · ESInstituto de Salud Carlos III · ESInstituto Murciano de Investigación Biosanitaria · ESSorbonne Université · FRUniversitat de Vic - Universitat Central de Catalunya · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThere are few therapeutic options available for patients with B-cell acute lymphoblastic leukemia (B-ALL) relapsing as CD19

methodsHere, we have developed and comprehensively characterized a novel CD22-CAR (clone hCD22.7) targeting a membrane-distal CD22 epitope and tested its cytotoxic effects against B-ALL cells both in in vitro and in vivo assays.

resultsConformational epitope mapping, cross-blocking, and molecular docking assays revealed that the hCD22.7 scFv is a high-affinity binding antibody which specifically binds to the ESTKDGKVP sequence, located in the Ig-like V-type domain, the most distal domain of CD22. We observed efficient killing of B-ALL cells in vitro, although the kinetics were dependent on the level of CD22 expression. Importantly, we show an efficient in vivo control of patients with B-ALL derived xenografts with diverse aggressiveness, coupled to long-term hCD22.7-CAR T cell persistence. Remaining leukemic cells at sacrifice maintained full expression of CD22, ruling out CAR pressure-mediated antigen loss. Finally, the immunogenicity capacity of this hCD22.7-scFv was very similar to that of other CD22 scFv previously used in adoptive T cell therapy.

conclusionsWe report a novel, high-affinity hCD22.7 scFv which targets a membrane-distal epitope of CD22. 4-1BB-based hCD22.7-CAR T cells efficiently eliminate clinically relevant B- CD22

Indexed as

AnimalsEpitopesHumansMaleMicePrecursor Cell Lymphoblastic Leukemia-LymphomaReceptors, Chimeric AntigenSialic Acid Binding Ig-like Lectin 2CD22 protein, humanEpitopesReceptors, Chimeric AntigenSialic Acid Binding Ig-like Lectin 2cell engineeringhematologic neoplasmsimmunotherapyreceptors, chimeric antigenT-lymphocytes

Identifiers

PMID32788237
PMCPMC7422657
OpenAlexW3048949182

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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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.