Evidence map›Paper›PMID 37890480›Full record

ArticleCell chemical biology2024

Bispecific antibody shuttles targeting CD98hc mediate efficient and long-lived brain delivery of IgGs.

Ghasidit Pornnoppadol, Layne G Bond, Michael J Lucas, Jennifer M Zupancic, Yun-Huai Kuo, Boya Zhang, Colin F Greineder, Peter M Tessier

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

Article in Cell chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
11.2field-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.

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

43 citing papers in PubMed, 49 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Ghasidit PornnoppadolDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Layne G BondBiointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Program in Chemical Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Michael J LucasDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Jennifer M ZupancicBiointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Yun-Huai KuoDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Boya ZhangBiointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA.
Colin F GreinederBiointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Emergency Medicine, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: coling@umich.edu.
Peter M TessierDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Program in Chemical Biology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: ptessier@umich.edu.
University of Michigan · US

Funding

TRAINING IN CLINICAL AND BASIC NEUROSCIENCET32NS007222 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Henry L Paulson · 1985 to 2026
$8.0M
CD98hc Brain Shuttles for Delivering Off-the-shelf Neuroprotective Antibodies in Alzheimer's DiseaseR01AG080016 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Colin Fred Greineder, Peter M Tessier · 2023 to 2026
$3.2M
Design and Evolution of Polyvalent Domain Antibodies Specific for Tau AggregatesRF1AG059723 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KANE, RAVI S., TESSIER, PETER M · 2018 to 2022
$2.4M
Structure-guided antibody targeting of pre-selected epitopes in amyloidogenic aggregatesR35GM136300 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESSIER, PETER M · 2020 to 2024
$1.5M
ICAM-1 targeted thrombomodulin: an experimental therapeutic for the Acute Respiratory Distress SyndromeK08HL130430 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI GREINEDER, COLIN FRED · 2016 to 2020
$665k
Efficient Brain Delivery of Neuroprotective TrkB Agonist Antibodies in Alzheimer’s Disease Using CD98hc Bispecific ShuttlesF32AG079576 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUCAS, MICHAEL JOHN · 2022 to 2023
$132k
NHLBI NIH HHS K08 HL130430NIA NIH HHS F32 AG079576NIA NIH HHS R01 AG080016NIA NIH HHS RF1 AG059723NIGMS NIH HHS R35 GM136300NINDS NIH HHS T32 NS007222
6 · The paper itself

Abstract

The inability of antibodies to penetrate the blood-brain barrier (BBB) is a key limitation to their use in diverse applications. One promising strategy is to deliver IgGs using a bispecific BBB shuttle, which involves fusing an IgG to a second affinity ligand that engages a cerebrovascular endothelial target and facilitates transport across the BBB. Nearly all prior efforts have focused on shuttles that target transferrin receptor (TfR-1) despite inherent delivery and safety challenges. Here, we report bispecific antibody shuttles that engage CD98hc, the heavy chain of the large neutral amino acid transporter (LAT1), and efficiently transport IgGs into the brain. Notably, CD98hc shuttles lead to much longer-lived brain retention of IgGs than TfR-1 shuttles while enabling more specific targeting due to limited CD98hc engagement in the brain parenchyma, which we demonstrate for IgGs that either agonize a neuronal receptor (TrkB) or target other endogenous cell-surface proteins on neurons and astrocytes.

Indexed as

Antibodies, BispecificBrainAstrocytesBiological TransportBlood-Brain BarrierAntibodies, Bispecific4F2astrocyteBBBBDNFblood-brain barrierneuronneurotrophinSLC3A2transferrin receptorTrkB

Identifiers

PMID37890480
PMCPMC10922565
OpenAlexW4387996290

What OpenQuestion holds

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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.