Evidence map›Paper›PMID 38477945›Full record

ArticleACS chemical biology2024

A Humanized Mouse Model Coupled with Computational Analysis Identifies Potent Glycolipid Agonist of Invariant NKT Cells.

Noemi A Saavedra-Avila, Natalia B Pigni, Donald R Caldwell, Florencia Chena-Becerra, Jose Intano, Tony W Ng, Divya Chennamadhavuni, Steven A Porcelli, José A Gascón, Amy R Howell

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
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

10 authors at 2 institutions in 2 countries.

Noemi A Saavedra-AvilaDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
Natalia B PigniDepartment of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.ORCID 0000-0003-4716-6377
Donald R CaldwellDepartment of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.
Florencia Chena-BecerraDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
Jose IntanoDepartment of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.
Tony W NgDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
Divya ChennamadhavuniDepartment of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.
Steven A PorcelliDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
José A GascónDepartment of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.ORCID 0000-0002-4176-9030
Amy R HowellDepartment of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.ORCID 0000-0003-1958-6411
University of Connecticut · USAlbert Einstein College of Medicine · US

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2M
Precision Targeting of CD1-Restricted iNKT Cells for Cancer ImmunotherapyR01AI045889 · NIAID · YESHIVA UNIVERSITY · PI Steven A Porcelli · 1999 to 2026
$9.3M
Harnessing NKT Cell Activation by GlycolipidsR01GM111849 · NIGMS · UNIVERSITY OF CONNECTICUT STORRS · PI HOWELL, AMY · 2019 to 2022
$2.1M
Bigfoot Multispectral High Speed Fluorescence Activated Cell SorterS10OD032169 · OD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI PORCELLI, STEVEN A · 2022 to 2022
$600k
Cytek Aurora Multiparameter Flow CytometerS10OD026833 · OD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI PORCELLI, STEVEN A · 2019 to 2019
$367k
NCI NIH HHS P30 CA013330NIAID NIH HHS R01 AI045889NIGMS NIH HHS R01 GM111849NIH HHS S10 OD026833NIH HHS S10 OD032169
6 · The paper itself

Abstract

Invariant natural killer T (iNKT) cells play an important role in many innate and adaptive immune responses, with potential applications in cancer immunotherapy. The glycolipid KRN7000, an α-galactosylceramide, potently activates iNKT cells but has shown limited anticancer effects in human clinical trials conducted so far. In spite of almost three decades of structure-activity relationship studies, no alternative glycolipid has yet emerged as a superior clinical candidate. One reason for the slow progress in this area is that standard mouse models do not accurately reflect the specific ligand recognition by human iNKT cells and their requirements for activation. Here we evaluated a series of KRN7000 analogues using a recently developed humanized mouse model that expresses a human αTCR chain sequence and human CD1d. In this process, a more stimulatory, previously reported but largely overlooked glycolipid was identified, and its activity was probed and rationalized via molecular simulations.

Indexed as

GalactosylceramidesGlycolipidsNatural Killer T-CellsAnimalsAntigens, CD1dHumansMiceAntigens, CD1dGalactosylceramidesGlycolipidsKRN 7000

Identifiers

PMID38477945
PMCPMC11075374
OpenAlexW4392748325

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.