Evidence map›Paper›PMID 37873222›Full record

ArticlebioRxiv : the preprint server for biology2023

IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers.

Xinyan Zhang, Qian Xiao, Longhui Zeng, Fawzaan Hashmi, Xiaolei Su

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

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

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Xinyan ZhangDepartment of Cell Biology, Yale School of Medicine, New Haven, CT 06520.
Qian XiaoDepartment of Cell Biology, Yale School of Medicine, New Haven, CT 06520.
Longhui ZengDepartment of Cell Biology, Yale School of Medicine, New Haven, CT 06520.
Fawzaan HashmiDepartment of Cell Biology, Yale School of Medicine, New Haven, CT 06520.
Xiaolei SuDepartment of Cell Biology, Yale School of Medicine, New Haven, CT 06520.ORCID 0000-0001-8696-7922
Yale University · USYale Cancer Center · US

Funding

Yale SPORE in Skin CancerP50CA121974 · NCI · YALE UNIVERSITY · PI MARCUS W BOSENBERG, Harriet M. Kluger · 2006 to 2026
$43.9M
Spatial Organization of Membrane SignalingR35GM138299 · NIGMS · YALE UNIVERSITY · PI SU, XIAOLEI · 2020 to 2024
$2.3M
NCI NIH HHS P50 CA121974NIGMS NIH HHS R35 GM138299
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR)-T cell-based therapies demonstrate remarkable efficacy for the treatment of otherwise intractable cancers, particularly B-cell malignancies. However, existing FDA-approved CAR-Ts are limited by low antigen sensitivity, rendering their insufficient targeting to low antigen-expressing cancers. To improve the antigen sensitivity of CAR-Ts, we engineered CARs targeting CD19, CD22, and HER2 by including intrinsically disordered regions (IDRs) that promote signaling condensation. The "IDR CARs" triggered enhanced membrane-proximal signaling in the CAR-T synapse, which led to an increased release of cytotoxic factors, a higher killing activity towards low antigen-expressing cancer cells in vitro, and an improved anti-tumor efficacy in vivo. No elevated tonic signaling was observed in IDR CAR-Ts. Together, we demonstrated IDRs as a new tool set to enhance CAR-T cytotoxicity and to broaden CAR-T's application to low antigen-expressing cancers.

Indexed as

CAR-TCD19CD22condensationEWSFUSHER2intrinsically disordered proteinintrinsically disordered regionTAF15

Identifiers

PMID37873222
PMCPMC10592880
OpenAlexW4387310062

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.