Evidence map›Paper›PMID 33234592›Full record

ArticleThe Journal of biological chemistry

Combinatorial CAR design improves target restriction.

Hakan Köksal, Pierre Dillard, Asta Juzeniene, Gunnar Kvalheim, Erlend B Smeland, June H Myklebust, Else Marit Inderberg, Sébastien Wälchli

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Determination of CAR T cell metabolism in an optimized protocol.Frontiers in bioengineering and biotechnology · 2023
    Article
  5. Review
  6. 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

8 authors at 1 institution in 1 country.

Hakan KöksalDepartment of Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway.
Pierre DillardDepartment of Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway.
Asta JuzenieneDepartment of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Gunnar KvalheimDepartment of Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway.
Erlend B SmelandDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; K.G. Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway.
June H MyklebustDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; K.G. Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway.
Else Marit InderbergDepartment of Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway.
Sébastien WälchliDepartment of Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway. Electronic address: sebastw@rr-research.no.
Oslo University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CAR T cells targeting the B lymphocyte antigen CD19 have led to remarkable clinical results in B cell leukemia and lymphoma but eliminate all B lineage cells, leading to increased susceptibility to severe infections. As malignant B cells will express either immunoglobulin (Ig) light chain κ or λ, we designed a second-generation CAR targeting Igκ, IGK CAR. This construct demonstrated high target specificity but displayed reduced efficacy in the presence of serum IgG. Since CD19 CAR is insensitive to serum IgG, we designed various combinatorial CAR constructs in order to maintain the CD19 CAR T cell efficacy, but with IGK CAR target selectivity. The Kz-19BB design, combining CD19 CAR containing a 4-1BB costimulatory domain with an IGK CAR containing a CD3zeta stimulatory domain, maintained the target specificity of IgK CAR and was resistant to the presence of soluble IgG. Our results demonstrate that a combinatorial CAR approach can improve target selectivity and efficacy.

Indexed as

Antigens, CD19B-LymphocytesCD28 AntigensCell Line, TumorHumansImmunotherapy, AdoptiveLymphomaReceptors, Antigen, T-CellReceptors, Chimeric AntigenT-LymphocytesAntigens, CD19CD28 AntigensReceptors, Antigen, T-CellReceptors, Chimeric AntigenB cell malignanciescell therapychimeric antigen receptor (CAR) T cellsimmunoglobulin kappa light chainimmunotherapy

Identifiers

PMID33234592
PMCPMC7948400
OpenAlexW3109503323

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.