Evidence map›Paper›PMID 39932788›Full record

ArticleThe Journal of clinical investigation2025

Rapamycin enhances CAR-T control of HIV replication and reservoir elimination in vivo.

Wenli Mu, Shallu Tomer, Jeffrey Harding, Nandita Kedia, Valerie Rezek, Ethan Cook, Vaibahavi Patankar, Mayra A Carrillo, Heather Martin, Hwee Ng and 4 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

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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

14 authors.

Wenli MuDivision of Hematology/Oncology, Department of Medicine, and.
Shallu TomerDivision of Hematology/Oncology, Department of Medicine, and.
Jeffrey HardingDivision of Hematology/Oncology, Department of Medicine, and.
Nandita KediaDivision of Hematology/Oncology, Department of Medicine, and.
Valerie RezekDivision of Hematology/Oncology, Department of Medicine, and.
Ethan CookDivision of Hematology/Oncology, Department of Medicine, and.
Vaibahavi PatankarDivision of Hematology/Oncology, Department of Medicine, and.
Mayra A CarrilloDivision of Hematology/Oncology, Department of Medicine, and.
Heather MartinDivision of Hematology/Oncology, Department of Medicine, and.
Hwee NgDivision of Hematology/Oncology, Department of Medicine, and.
Li WangDivision of Hematology/Oncology, Department of Medicine, and.
Matthew D MarsdenDepartment of Microbiology & Molecular Genetics and.
Scott G KitchenDivision of Hematology/Oncology, Department of Medicine, and.
Anjie ZhenDivision of Hematology/Oncology, Department of Medicine, and.

Funding

Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZACK, JEROME A. · 1991 to 2018
$39.9M
UCLA-CDU CFARP30AI152501 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SCOTT G KITCHEN · 2022 to 2026
$15.6M
Viral Immunology CoreU19AI149504 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHEN, IRVIN S.Y., KITCHEN, SCOTT G · 2020 to 2024
$14.3M
Induction of autophagy to enhance CAR-T cells in HIV cure approachesR01AI172727 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARSDEN, MATTHEW DAVID, ZHEN, ANJIE · 2022 to 2025
$3.9M
Targeting autophagy to reduce inflammasome-mediated inflammation and immune dysfunction in HIV and methamphetamine useR01DA059873 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jennifer Fulcher, Ye Zhang · 2024 to 2026
$2.1M
Define the effects and mechanism of THC and CBD on IFN-I mediated inflammation and immune dysfunction during HIV infectionR01DA052841 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KITCHEN, SCOTT G, ZHEN, ANJIE · 2020 to 2024
$1.9M
Role of persistent type I IFN signaling in immune suppression and tumorigenesis during chronic HIV infectionR01CA239261 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KITCHEN, SCOTT G · 2019 to 2023
$1.8M
Targeting Autophagy to Restore Anti-HIV T Cell ResponseR21AI140866 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHEN, ANJIE · 2018 to 2019
$429k
NCI NIH HHS R01 CA239261NIAID NIH HHS P30 AI028697NIAID NIH HHS P30 AI152501NIAID NIH HHS R01 AI172727NIAID NIH HHS R21 AI140866NIAID NIH HHS U19 AI149504NIDA NIH HHS R01 DA052841NIDA NIH HHS R01 DA059873
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cell therapy shows promise for various diseases. Our studies in humanized mice and nonhuman primates demonstrate that hematopoietic stem cells (HSCs) modified with anti-HIV CAR achieve lifelong engraftment, providing functional antiviral CAR-T cells that reduce viral rebound after antiretroviral therapy (ART) withdrawal. However, T cell exhaustion due to chronic immune activation remains a key obstacle to sustained CAR-T efficacy, necessitating additional measures to achieve functional cure. We recently showed that low-dose rapamycin treatment reduced inflammation and improved anti-HIV T cell function in HIV-infected humanized mice. Here, we report that rapamycin improved CAR-T cell function both in vitro and in vivo. In vitro treatment with rapamycin enhanced CAR-T cell mitochondrial respiration and cytotoxicity. In vivo treatment with low-dose rapamycin in HIV-infected, CAR-HSC mice decreased chronic inflammation, prevented exhaustion of CAR-T cells, and improved CAR-T control of viral replication. RNA-sequencing analysis of CAR-T cells from humanized mice showed that rapamycin downregulated multiple checkpoint inhibitors and upregulated key survival genes. Mice treated with CAR-HSCs and rapamycin had delayed viral rebound after ART and reduced HIV reservoir compared with those treated with CAR-HSCs alone. These findings suggest that HSC-based anti-HIV CAR-T cells combined with rapamycin treatment are a promising approach for treating persistent inflammation and improving immune control of HIV replication.

Indexed as

HIV-1HIV InfectionsImmunotherapy, AdoptiveReceptors, Chimeric AntigenSirolimusVirus ReplicationAnimalsHumansMiceReceptors, Chimeric AntigenSirolimusAIDS/HIVImmunologyImmunotherapyT cells

Identifiers

PMID39932788
PMCPMC11957703

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Registered trials

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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.