Evidence map›Paper›PMID 22360982›Full record

ArticleJournal of the American College of Surgeons2012

Ex vivo interleukin-12-priming during CD8(+) T cell activation dramatically improves adoptive T cell transfer antitumor efficacy in a lymphodepleted host.

Mark P Rubinstein, Colleen A Cloud, Tracy E Garrett, Caitlin J Moore, Kristina M Schwartz, C Bryce Johnson, David H Craig, Mohamed L Salem, Chrystal M Paulos, David J Cole

Abstract readEvaluation Study
In one paragraph

Article in Journal of the American College of Surgeons, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

24 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. B cells imprint adoptively transferred CD8Journal for immunotherapy of cancer · 2022
    Article
  6. Brief in vitro IL-12 conditioning of CD8Cancer immunology, immunotherapy : CII · 2021
    Review
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  8. Review
  9. Review
  10. Article
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  12. Review
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  20. Review
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.

Mark P RubinsteinDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. markrubinstein@musc.edu
Colleen A Cloud
Tracy E Garrett
Caitlin J Moore
Kristina M Schwartz
C Bryce Johnson
David H Craig
Mohamed L Salem
Chrystal M Paulos
David J Cole
Medical University of South Carolina · USTanta University · EG

Funding

TCR TRANSDUCED CDB T CELLS FOR ADOPTIVE IMMUNOTHERAPYP01CA154778 · NCI · LOYOLA UNIVERSITY CHICAGO · PI NISHIMURA, MICHAEL I. · 2011 to 2015
$15.4M
Targeting Early Activated T cells for Adoptive TherapyR01CA083672 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI COLE, DAVID J · 2001 to 2010
$2.8M
NCI NIH HHS 1R01CA083672-09NCI NIH HHS P01 CA154778NCI NIH HHS R01 CA083672
6 · The paper itself

Abstract

backgroundClinical application of adoptive T cell therapy has been hindered by an inability to generate adequate numbers of nontolerized, functionally active, tumor-specific T cells, which can persist in vivo. In order to address this, we evaluated the impact of interleukin (IL)-12 signaling during tumor-specific CD8(+) T cell priming in terms of persistence and antitumor efficacy using an established B16 melanoma tumor adoptive therapy model. STUDY

designB6 mice were injected subcutaneously with B16 melanoma tumor cells. On day 12 of tumor growth, mice were preconditioned with cyclophosphamide (4mg dose, intraperitoneally), and 1 day later were treated by adoptive transfer of tumor-specific pmel-1 CD8(+) T cells primed ex vivo 3 days earlier with both IL-12 and antigen (hGP100(25-33) peptide) or antigen only. Tumors were measured biweekly, and infused donor T cells were analyzed for persistence, localization to the tumor, phenotype, and effector function.

resultsAdoptive transfer of tumor-specific CD8(+) T cells primed with IL-12 was significantly more effective in reducing tumor burden in mice preconditioned with cyclophosphamide compared with transfer of T cells primed without IL-12. This enhanced antitumor response was associated with increased frequencies of infused T cells in the periphery and tumor as well as elevated expression of effector molecules including granzyme B and interferon-γ (IFNγ).

conclusionsOur findings demonstrate that ex vivo priming of tumor-specific CD8(+) T cells with IL-12 dramatically improves their in vivo persistence and therapeutic ability on transfer to tumor-bearing mice. These findings can be directly applied as novel clinical trial strategies.

Indexed as

Lymphocyte ActivationAnimalsCD8-Positive T-LymphocytesCell Line, TumorCyclophosphamideFemaleFlow CytometryImmunosuppressive AgentsImmunotherapy, AdoptiveInterleukin-12MaleMelanomaMiceMice, Inbred C57BLTreatment OutcomeTumor BurdenCyclophosphamideImmunosuppressive AgentsInterleukin-12

Identifiers

PMID22360982
PMCPMC3429131
OpenAlexW2053665503

What OpenQuestion holds

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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.