Evidence map›Paper›PMID 23433400›Full record

ArticleBMC cancer2013

Targeting and killing of glioblastoma with activated T cells armed with bispecific antibodies.

Ian M Zitron, Archana Thakur, Oxana Norkina, Geoffrey R Barger, Lawrence G Lum, Sandeep Mittal

Registry-linked trialAbstract read
In one paragraph

Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02662348 (T Cell Mediated Adaptive Therapy for Her2-positive Neoplasms of Digestive System), which is not on this map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
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.

NCT02662348 phase1unknown statusnot on this mapstarted 2016, after this paper: background citation

T Cell Mediated Adaptive Therapy for Her2-positive Neoplasms of Digestive System

TypeinterventionalSponsorYi MiaoRan2016 to 2017Enrolled6ConditionsEsophageal Cancer, Gastric Cancer, Pancreatic Cancer, Liver CancerArmsRecombinant Human Interleukin-2, HER2Bi-Armed T Cells
3 · Its place in the literature

Who cites it

28 citing papers in PubMed.

  1. Review
  2. Article
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  6. Review
  7. Article
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  16. Article
  17. mRNA: A Novel Avenue to Antibody Therapy?Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Review
  18. T cell-redirecting bispecific antibodies in cancer immunotherapy: recent advances.Journal of cancer research and clinical oncology · 2019
    Review
  19. Article
  20. mRNA as novel technology for passive immunotherapy.Cellular and molecular life sciences : CMLS · 2019
    Review
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.

Ian M ZitronDepartment of Neurosurgery, Wayne State University, Karmanos Cancer Institute, Detroit, MI, USA.
Archana Thakur
Oxana Norkina
Geoffrey R Barger
Lawrence G Lum
Sandeep Mittal

Funding

Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI PAUL M STEMMER · 1985 to 2026
$68.4M
Breast Cancer Treatment with Antibody Targeted T CellsR01CA092344 · NCI · WAYNE STATE UNIVERSITY · PI LUM, LAWRENCE G · 2002 to 2012
$4.6M
Enhancing neoadjuvant chemotherpay responses with targeted T cellsR01CA140314 · NCI · WAYNE STATE UNIVERSITY · PI BEPLER, GEROLD · 2010 to 2015
$2.5M
NCI NIH HHS P30 CA022453NCI NIH HHS P30 CA022453-25NCI NIH HHS R01 CA092344NCI NIH HHS R01 CA 140314NCI NIH HHS R01 CA 92344
6 · The paper itself

Abstract

backgroundSince most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2.

methodsATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3 × anti-HER2/neu (HER2Bi) and/or anti-CD3 × anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and 51Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines.

resultsEGFRBi-armed ATC killed up to 85% of U87, U118, and U251 targets at effector:target ratios (E:T) ranging from 1:1 to 25:1. Engagement of tumor by EGFRBi-armed ATC induced Th1 and Th2 cytokine secretion by armed ATC. HER2Bi-armed ATC exhibited comparable cytotoxicity against U118 and U251, but did not kill HER2-negative U87 cells. HER2Bi- or EGFRBi-armed ATC exhibited 50--80% cytotoxicity against four primary glioblastoma lines as well as a temozolomide (TMZ)-resistant variant of U251. Both CD133- and CD133+ subpopulations were killed by armed ATC. Targeting both HER2Bi and EGFRBi simultaneously showed enhanced efficacy than arming with a single BiAb. Armed ATC maintained effectiveness after irradiation and in the presence of TMZ at a therapeutic concentration and were capable of killing multiple targets.

conclusionHigh-grade gliomas are suitable for specific targeting by armed ATC. These data, together with additional animal studies, may provide the preclinical support for the use of armed ATC as a valuable addition to current treatment regimens.

Indexed as

Analysis of VarianceAntibodies, BispecificBrain NeoplasmsCD3 ComplexCell LineageCytokinesCytotoxicity Tests, ImmunologicGlioblastomaHumansImmunotherapyLymphocyte ActivationT-Lymphocytes, CytotoxicAntibodies, BispecificCD3 ComplexCytokines

Identifiers

PMID23433400
PMCPMC3599512

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Registered trials

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.