Evidence map›Paper›PMID 34253928›Full record

ArticleNature medicine2021

Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis.

Nicholas A Vitanza, Adam J Johnson, Ashley L Wilson, Christopher Brown, Jason K Yokoyama, Annette Künkele, Cindy A Chang, Stephanie Rawlings-Rhea, Wenjun Huang, Kristy Seidel and 11 more

2 registry-linked trialsAbstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 229 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
229citing papers in PubMed, 6 pooled it
19.5field-weighted citation impact, top 1% 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.

NCT03500991 phase1active not recruitingnot on this map

Phase 1 Study of HER2-Specific CAR T Cell Locoregional Immunotherapy for HER2 Positive Recurrent/Refractory Pediatric Central Nervous System Tumors

TypeinterventionalSponsorSeattle Children's HospitalRan2018 to 2039Enrolled10ConditionsCentral Nervous System Tumor, Pediatric, Glioma, Ependymoma, MedulloblastomaArmsHER2-specific chimeric antigen receptor (CAR) T cell
NCT05577091 phase1recruitingnot on this mapstarted 2023, after this paper: background citation

Phase 1 Study of Autologous Tris-CAR-T Cell Locoregional Immunotherapy for Recurrent Glioblastoma

TypeinterventionalSponsorBeijing Tiantan HospitalRan2023 to 2032Enrolled10ConditionsRecurrent GlioblastomaArmsInverse correlated dual-target, truncated IL7Ra modified CAR -expressing autologous T-lymphocytes.
3 · Its place in the literature

Who cites it

229 citing papers in PubMed, 6 syntheses or guidelines pooled it, 297 citations in OpenAlex.

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169 more citing papers are in PubMed but not listed here.

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

21 authors at 2 institutions in 2 countries.

Nicholas A VitanzaThe Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA. nicholas.vitanza@seattlechildrens.org.ORCID http://orcid.org/0000-0002-3966-4985
Adam J JohnsonThe Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-9967-8959
Ashley L WilsonThe Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
Christopher BrownSeattle Children's Therapeutics, Seattle, WA, USA.
Jason K YokoyamaThe Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
Annette KünkeleDepartment of Pediatric Oncology and Hematology, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0002-8406-5412
Cindy A ChangOffice of Animal Care, Seattle Children's Research Institute, Seattle, WA, USA.
Stephanie Rawlings-RheaThe Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
Wenjun HuangThe Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-8948-7262
Kristy SeidelSeattle Children's Therapeutics, Seattle, WA, USA.
Catherine M AlbertDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of Washington, Seattle, WA, USA.
Navin PintoDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-8775-6710
Juliane GustDepartment of Neurology, University of Washington, Seattle, WA, USA.
Laura S FinnDepartment of Laboratories, Seattle Children's Hospital, Seattle, WA, USA.
Jeffrey G OjemannDivision of Neurosurgery, Department of Neurological Surgery, Seattle Children's Hospital, Seattle, WA, USA.
Jason WrightDepartment of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
Rimas J OrentasThe Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
Michael BaldwinThe Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
Rebecca A GardnerThe Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
Michael C Jensen *Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-7477-3063
Julie R Park *Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-6777-9165
Seattle Children's Hospital · USUniversity of Washington · US

Funding

Prospective evaluation of barriers to patient referral and enrollment in emerging cellular therapy trials: determining methods and structure to improve equity in future trial designU01TR002487 · NCATS · SEATTLE CHILDREN'S HOSPITAL · PI PARK, JULIE R, RAMSEY, BONNIE W · 2018 to 2022
$7.2M
NCATS NIH HHS U01 TR002487
6 · The paper itself

Abstract

Locoregional delivery of chimeric antigen receptor (CAR) T cells has resulted in objective responses in adults with glioblastoma, but the feasibility and tolerability of this approach is yet to be evaluated for pediatric central nervous system (CNS) tumors. Here we show that engineering of a medium-length CAR spacer enhances the therapeutic efficacy of human erb-b2 receptor tyrosine kinase 2 (HER2)-specific CAR T cells in an orthotopic xenograft medulloblastoma model. We translated these findings into BrainChild-01 ( NCT03500991 ), an ongoing phase 1 clinical trial at Seattle Children's evaluating repetitive locoregional dosing of these HER2-specific CAR T cells to children and young adults with recurrent/refractory CNS tumors, including diffuse midline glioma. Primary objectives are assessing feasibility, safety and tolerability; secondary objectives include assessing CAR T cell distribution and disease response. In the outpatient setting, patients receive infusions via CNS catheter into either the tumor cavity or the ventricular system. The initial three patients experienced no dose-limiting toxicity and exhibited clinical, as well as correlative laboratory, evidence of local CNS immune activation, including high concentrations of CXCL10 and CCL2 in the cerebrospinal fluid. This interim report supports the feasibility of generating HER2-specific CAR T cells for repeated dosing regimens and suggests that their repeated intra-CNS delivery might be well tolerated and activate a localized immune response in pediatric and young adult patients.

Indexed as

Antigens, CD19Chemokine CCL2Chemokine CXCL10Erb-b2 Receptor Tyrosine KinasesFemaleGlioblastomaHumansImmunityImmunotherapy, AdoptiveKaplan-Meier EstimateMaleNeoplasm Recurrence, LocalReceptors, Antigen, T-CellReceptors, Chimeric AntigenT-LymphocytesXenograft Model Antitumor AssaysAntigens, CD19CCL2 protein, humanChemokine CCL2Chemokine CXCL10CXCL10 protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesReceptors, Antigen, T-CellReceptors, Chimeric Antigen

Identifiers

PMID34253928
OpenAlexW3178970276

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.