Evidence map›Paper›PMID 36318382›Full record

ArticleBreast cancer research and treatment2023

EGFR as a potent CAR T target in triple negative breast cancer brain metastases.

Siddharth Subham, John D Jeppson, Colette Worcester, Bryan Schatmeyer, Jie Zhao, Rashna Madan, Nelli S Lakis, Bruce F Kimler, Joseph P McGuirk, Ronald C Chen and 2 more

Open access · greenAbstract read
In one paragraph

Article in Breast cancer research and treatment, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

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  12. New T-Cell Therapies for Brain Metastasis, CD133 in the Driver's Seat.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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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

12 authors at 3 institutions in 1 country.

Siddharth SubhamDepartment of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS, USA.
John D JeppsonDepartment of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS, USA.
Colette WorcesterDepartment of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS, USA.
Bryan SchatmeyerDepartment of Neurosurgery, University of Kansas Medical Center, Kansas City, KS, USA.
Jie ZhaoDepartment of Cancer Biology, University of Kansas Cancer Center, Kansas City, KS, USA.
Rashna MadanDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
Nelli S LakisDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
Bruce F KimlerDepartment of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS, USA.
Joseph P McGuirkDepartment of Hematology and Stem Cell Transplantation, University of Kansas Medical Center, Kansas City, KS, USA.
Ronald C ChenDepartment of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS, USA.
Shane R SteckleinDepartment of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS, USA.
David AkhavanDepartment of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS, USA. dakhavan@kumc.edu.ORCID http://orcid.org/0000-0001-9733-6069
The University of Kansas Cancer Center · USUniversity of Kansas Medical Center · USUniversity of Kansas · US

Funding

Using Integrated Omics to Identify Dysfunctional Genetic Mechanisms Influencing Schizophrenia and Sleep DisturbancesP20GM130423 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Kalyani Pyaram, Steven Allan Soper · 2019 to 2026
$21.5M
Design of a Novel Nanocarrier Technology to Drug-Load CAR T cellsR01CA284065 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI David Akhavan, Stefan H Bossmann · 2023 to 2026
$2.3M
NCI NIH HHS R01 CA284065
6 · The paper itself

Abstract

purposeThere is currently no curative treatment for patients diagnosed with triple-negative breast cancer brain metastases (TNBC-BM). CAR T cells hold potential for curative treatment given they retain the cytolytic activity of a T cell combined with the specificity of an antibody. In this proposal we evaluated the potential of EGFR re-directed CAR T cells as a therapeutic treatment against TNBC cells in vitro and in vivo.

methodsWe leveraged a TNBC-BM tissue microarray and a large panel of TNBC cell lines and identified elevated epidermal growth factor receptor (EGFR) expression. Next, we designed a second-generation anti-EGFR CAR T construct incorporating a clinically relevant mAb806 tumor specific single-chain variable fragment (scFv) and intracellular 4-1BB costimulatory domain and CD3ζ using a lentivirus system and evaluated in vitro and in vivo anti-tumor activity.

resultsWe demonstrate EGFR is enriched in TNBC-BM patient tissue after neurosurgical resection, with six of 13 brain metastases demonstrating both membranous and cytoplasmic EGFR. Eleven of 13 TNBC cell lines have EGFR surface expression ≥ 85% by flow cytometry. EGFR806 CAR T treated mice effectively eradicated TNBC-BM and enhanced mouse survival (log rank p < 0.004).

conclusionOur results demonstrates anti-tumor activity of EGFR806 CAR T cells against TNBC cells in vitro and in vivo. Given EGFR806 CAR T cells are currently undergoing clinical trials in primary brain tumor patients without obvious toxicity, our results are immediately actionable against the TNBC-BM patient population.

Indexed as

Brain NeoplasmsReceptors, Chimeric AntigenTriple Negative Breast NeoplasmsAnimalsCell Line, TumorErbB ReceptorsHumansMiceEGFR protein, humanErbB ReceptorsReceptors, Chimeric AntigenBrain metastasesBreast cancerCAR TEGFRTNBC

Identifiers

PMID36318382
PMCPMC10987173
OpenAlexW4307838181

What OpenQuestion holds

Textmetadata
LicenceTDM
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.