Evidence map›Paper›PMID 22511873›Full record

Trial reportPLoS pathogens2012

In vivo suppression of HIV by antigen specific T cells derived from engineered hematopoietic stem cells.

Scott G Kitchen, Bernard R Levin, Gregory Bristol, Valerie Rezek, Sohn Kim, Christian Aguilera-Sandoval, Arumugam Balamurugan, Otto O Yang, Jerome A Zack

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

53 citing papers in PubMed, 83 citations in OpenAlex.

  1. Beyond Oncology: Exploring the Expanding Role of CAR T Cell Therapy in Autoimmune and Infectious Diseases-A Systematic Review.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
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  12. Chronic virus infection drives CD8 T cell-mediated thymic destruction and impaired negative selection.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  13. Engineering CAR T Cells to Target the HIV Reservoir.Frontiers in cellular and infection microbiology · 2020
    Review
  14. Lentiviral Vector-Based Dendritic Cell Vaccine Suppresses HIV Replication in Humanized Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Article
  15. Nanotechnology approaches to eradicating HIV reservoirs.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019
    Review
  16. IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
    Article
  17. CD8Immunity · 2018
    Article
  18. Review
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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

9 authors at 2 institutions in 1 country.

Scott G KitchenDivision of Hematology-Oncology, The David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America. skitchen@ucla.edu
Bernard R Levin
Gregory Bristol
Valerie Rezek
Sohn Kim
Christian Aguilera-Sandoval
Arumugam Balamurugan
Otto O Yang
Jerome A Zack
University of California, Los Angeles · USBlack AIDS Institute · US

Funding

Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9M
HIV-1 Excape from Inhibiton by Cytotoxic T LymphocytesR01AI043203 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, OTTO O · 1998 to 2012
$4.6M
Targeting HIV Reservoirs in vitro and in vivoR01AI070010 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZACK, JEROME A. · 2006 to 2014
$3.7M
The role of CD4 in macrophage differentiation and functionR01AI078806 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KITCHEN, SCOTT G · 2009 to 2013
$1.9M
NIAID NIH HHS P30 AI028697NIAID NIH HHS P30 AI28697NIAID NIH HHS R01 AI043203NIAID NIH HHS R01AI043203NIAID NIH HHS R01 AI070010NIAID NIH HHS R01AI070010NIAID NIH HHS R01 AI078806NIAID NIH HHS R01AI078806
6 · The paper itself

Abstract

The HIV-specific cytotoxic T lymphocyte (CTL) response is a critical component in controlling viral replication in vivo, but ultimately fails in its ability to eradicate the virus. Our intent in these studies is to develop ways to enhance and restore the HIV-specific CTL response to allow long-term viral suppression or viral clearance. In our approach, we sought to genetically manipulate human hematopoietic stem cells (HSCs) such that they differentiate into mature CTL that will kill HIV infected cells. To perform this, we molecularly cloned an HIV-specific T cell receptor (TCR) from CD8+ T cells that specifically targets an epitope of the HIV-1 Gag protein. This TCR was then used to genetically transduce HSCs. These HSCs were then introduced into a humanized mouse containing human fetal liver, fetal thymus, and hematopoietic progenitor cells, and were allowed to differentiate into mature human CD8+ CTL. We found human, HIV-specific CTL in multiple tissues in the mouse. Thus, genetic modification of human HSCs with a cloned TCR allows proper differentiation of the cells to occur in vivo, and these cells migrate to multiple anatomic sites, mimicking what is seen in humans. To determine if the presence of the transgenic, HIV-specific TCR has an effect on suppressing HIV replication, we infected with HIV-1 mice expressing the transgenic HIV-specific TCR and, separately, mice expressing a non-specific control TCR. We observed significant suppression of HIV replication in multiple organs in the mice expressing the HIV-specific TCR as compared to control, indicating that the presence of genetically modified HIV-specific CTL can form a functional antiviral response in vivo. These results strongly suggest that stem cell based gene therapy may be a feasible approach in the treatment of chronic viral infections and provide a foundation towards the development of this type of strategy.

Indexed as

Cell EngineeringGenetic TherapyAnimalsCD8-Positive T-LymphocytesFemaleHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHIV-1HIV Core Protein p24HIV InfectionsHumansMaleMiceMice, TransgenicReceptors, Antigen, T-CellTransplantation, HeterologousHIV Core Protein p24p24 protein, Human Immunodeficiency Virus Type 1Receptors, Antigen, T-Cell

Identifiers

PMID22511873
PMCPMC3325196
OpenAlexW2073001017

What OpenQuestion holds

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LicenceCC BY
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.