Evidence map›Paper›PMID 38685487›Full record

ArticleClinical and translational medicine2024

Identification and characterisation of novel CAR-T cells to target IL13Rα2 positive human glioma in vitro and in vivo.

Pamela Leland, Heba Degheidy, Ashley Lea, Steven R Bauer, Raj K Puri, Bharat H Joshi

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

7 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

6 authors at 4 institutions in 1 country.

Pamela Leland *Tumor Vaccine and Biotechnology Branch, Division of Cell Therapy II, Silver Spring, Maryland, USA.
Heba DegheidyCellular and Tissue Therapy Branch, Office of Cellular Therapy & Human Tissues, Office of Therapeutic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, White Oak, Silver Spring, Maryland, USA.
Ashley LeaTumor Vaccine and Biotechnology Branch, Division of Cell Therapy II, Silver Spring, Maryland, USA.
Steven R BauerCellular and Tissue Therapy Branch, Office of Cellular Therapy & Human Tissues, Office of Therapeutic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, White Oak, Silver Spring, Maryland, USA.
Raj K PuriTumor Vaccine and Biotechnology Branch, Division of Cell Therapy II, Silver Spring, Maryland, USA.
Bharat H JoshiTumor Vaccine and Biotechnology Branch, Division of Cell Therapy II, Silver Spring, Maryland, USA.ORCID 0000-0001-5246-3881
National Labor College · USCenter for Biologics Evaluation and Research · USForest Institute · USIntegrated BioTherapeutics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPreviously, we discovered that human solid tumours, but not normal human tissues, preferentially overexpress interleukin-13Receptor alpha2, a high binding receptor for IL-13. To develop novel anti-cancer approaches, we constructed a chimeric antigen receptor construct using a high binding and codon optimised scFv-IL-13Rα2 fragment fused with CD3ζ and co-stimulatory cytoplasmic domains of CD28 and 4-1BB.

methodsWe developed a scFv clone, designated 14-1, by biopanning the bound scFv phages using huIL-13Rα2Fc chimeric protein and compared its binding with our previously published clone 4-1. We performed bioinformatic analyses for complementary determining regions (CDR) framework and residue analyses of the light and heavy chains. This construct was packaged with helper plasmids to produce CAR-lentivirus and transduced human Jurkat T or activated T cells from peripheral blood mononuclear cells (PBMCs) to produce CAR-T cells and tested for their quality attributes in vitro and in vivo. Serum enzymes including body weight from non-tumour bearing mice were tested for assessing general toxicity of CAR-T cells.

resultsThe binding of 14-1 clone is to IL-13Rα2Fc-chimeric protein is ∼5 times higher than our previous clone 4-1. The 14-1-CAR-T cells grew exponentially in the presence of cytokines and maintained phenotype and biological attributes such as cell viability, potency, migration and T cell activation. Clone 14-1 migrated to IL-13Rα2Fc and cell free supernatants only from IL-13Rα2+ve confluent glioma tumour cells in a chemotaxis assay. scFv-IL-13Rα2-CAR-T cells specifically killed IL-13Rα2+ve but not IL-13Rα2-ve tumour cells in vitro and selectively caused significant release of IFN-γ only from IL-13Rα2+ve co-cultures. These CAR-T cells regressed IL-13Rα2+ve glioma xenografts in vivo without any general toxicity. In contrast, the IL-13Rα2 gene knocked-down U251 and U87 xenografts failed to respond to the CAR-T therapy.

conclusionTaken together, we conclude that the novel scFv-IL-13Rα2 CAR-T cell therapy may offer an effective therapeutic option after designing a careful pre-clinical and clinical study.

Indexed as

GliomaInterleukin-13 Receptor alpha2 SubunitAnimalsDisease Models, AnimalHumansImmunotherapy, AdoptiveMiceReceptors, Chimeric AntigenIL13RA2 protein, humanInterleukin-13 Receptor alpha2 SubunitReceptors, Chimeric AntigenCAR‐T cell therapygenetically engineered T cellsIL‐13Rα2immunotherapysingle‐chain variable fragment

Identifiers

PMID38685487
PMCPMC11058282
OpenAlexW4396517666

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.