Evidence map›Paper›PMID 33659980›Full record

ArticleNeuro-oncology2021

Enhanced brain delivery and therapeutic activity of trastuzumab after blood-brain barrier opening by NEO100 in mouse models of brain-metastatic breast cancer.

Weijun Wang, Haiping He, Nagore I Marín-Ramos, Shan Zeng, Steven D Swenson, Hee-Yeon Cho, Jie Fu, Paul M Beringer, Josh Neman, Ligang Chen and 2 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.4field-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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Weijun WangDepartment of Neurological Surgery, University of Southern California, Los Angeles, California, USA.ORCID 0000-0002-7430-5937
Haiping HeDepartment of Neurosurgery, Luzhou, China.
Nagore I Marín-RamosDepartment of Neurological Surgery, University of Southern California, Los Angeles, California, USA.
Shan ZengDepartment of Neurosurgery, Luzhou, China.
Steven D SwensonDepartment of Neurological Surgery, University of Southern California, Los Angeles, California, USA.
Hee-Yeon ChoDepartment of Neurological Surgery, University of Southern California, Los Angeles, California, USA.
Jie FuDepartment of Neurology Affiliated Hospital of Southwest Medical University, Luzhou, China.
Paul M BeringerDepartment of Clinical Pharmacy, Los Angeles, California, USA.
Josh NemanDepartment of Neurological Surgery, University of Southern California, Los Angeles, California, USA.
Ligang ChenDepartment of Neurosurgery, Luzhou, China.
Axel H SchönthalDepartment of Microbiology and Immunology, University of Southern California, Los Angeles, California, USA.
Thomas C ChenDepartment of Neurological Surgery, University of Southern California, Los Angeles, California, USA.
University of Southern California · USAffiliated Hospital of Southwest Medical University · CN

Funding

Small Animal Photoacoustic Imaging Unit: Integrating Optical Imaging with High FrS10OD018096 · OD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CONTI, PETER STEPHEN · 2014 to 2014
$599k
IVIS Spectrum Optical Imaging Core ResourceS10OD021785 · OD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CONTI, PETER STEPHEN · 2017 to 2017
$408k
Innovative Nose-to-Brain Anticancer Drug Transport Facilitated by NEO100R41CA217551 · NCI · NEONC TECHNOLOGIES, INC. · PI CHEN, THOMAS C., WANG , WEIJUN · 2018 to 2019
$301k
NCI NIH HHS R41 CA217551NIH HHS S10 OD018096NIH HHS S10 OD021785
6 · The paper itself

Abstract

backgroundThe antitumor efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapies, such as humanized monoclonal antibody trastuzumab (Herceptin®, Roche), in patients with breast-to-brain cancer metastasis is hindered by the low permeability of the blood-brain barrier (BBB). NEO100 is a high-purity version of the natural monoterpene perillyl alcohol, produced under current good manufacturing practice (cGMP) regulations, that was shown previously to reversibly open the BBB in rodent models. Here we investigated whether NEO100 could enable brain entry of trastuzumab to achieve greater therapeutic activity.

methodsAn in vitro BBB, consisting of human astrocytes and brain endothelial cells, was used to determine trastuzumab penetration in the presence or absence of NEO100. For in vivo studies, we administered intravenous (IV) trastuzumab or the trastuzumab-drug conjugate ado-trastuzumab emtansine (T-DM1; Kadcyla®, Roche), to mouse models harboring intracranial HER2+ breast cancer, with or without BBB opening via IA NEO100. Brain and tumor tissues were examined for the presence of trastuzumab and infiltration of immune cells. Therapeutic impact was evaluated based on overall survival.

resultsNEO100 greatly increased trastuzumab penetration across an in vitro BBB. In vivo, IA NEO100-mediated BBB opening resulted in brain tumor-selective accumulation of trastuzumab, without detectable presence in normal brain tissue, along with increased presence of immune cell populations. IV delivery of trastuzumab or T-DM1 achieved significantly greater overall survival of tumor-bearing mice when combined with IA NEO100.

conclusionIA NEO100 facilitates brain tumor entry of trastuzumab and T-DM1 and significantly enhances their therapeutic efficacy, along with increased antibody-dependent immune cell recruitment.

Indexed as

Brain NeoplasmsBreast NeoplasmsAnimalsBlood-Brain BarrierBrainEndothelial CellsErb-b2 Receptor Tyrosine KinasesFemaleHumansMiceMonoterpenesTrastuzumabErb-b2 Receptor Tyrosine KinasesMonoterpenesperillyl alcoholTrastuzumabblood-brain barrierbrain metastasisHER2+ breast cancerHerceptinKadcylaperillyl alcohol

Identifiers

PMID33659980
PMCPMC8485439
OpenAlexW3135831000

What OpenQuestion holds

Textmetadata
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.