Evidence map›Paper›PMID 22354001›Full record

ArticleBlood2012

Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning.

Hollie J Pegram, James C Lee, Erik G Hayman, Gavin H Imperato, Thomas F Tedder, Michel Sadelain, Renier J Brentjens

Open access · greenAbstract readEvaluation Study
In one paragraph

Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 427 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
427citing papers in PubMed, 1 pooled it
18.0field-weighted citation impact, top 1% 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

427 citing papers in PubMed, 1 synthesis or guideline pooled it, 672 citations in OpenAlex.

  1. Pooled it
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  11. Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  12. LRRC15-CAR T Cells for the Treatment of Osteosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
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367 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Hollie J PegramDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
James C Lee
Erik G Hayman
Gavin H Imperato
Thomas F Tedder
Michel Sadelain
Renier J Brentjens
Memorial Sloan Kettering Cancer Center · USDuke University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Yessinia autotransporters (Yaps): Structure, function, and host responseU54AI057157 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEMPOWSKI, GREGORY D · 2003 to 2013
$91.4M
Supplement - Inflammatory Triggers in B Cell AutoimmunityU19AI056363 · NIAID · DUKE UNIVERSITY · PI ST. CLAIR, EUGENE WILLIAM · 2003 to 2017
$35.3M
TUMORICIDAL FUNCTIONS OF T LYMPHOCYTES IN PSMA TUMORSP01CA059350 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SADELAIN, MICHEL WJ · 1992 to 2012
$21.4M
Adoptive Immunotherapy of Cancer with IL-12 Secreting Tumor-Targeted T cellsR01CA138738 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI BRENTJENS, RENIER JOSEPH · 2009 to 2013
$3.9M
Genetic Targeting of T cells to B cell malignanciesK08CA095152 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI BRENTJENS, RENIER JOSEPH · 2003 to 2005
$403k
Howard Hughes Medical InstituteNCI NIH HHS CA059350NCI NIH HHS CA08748NCI NIH HHS CA138738NCI NIH HHS CA95152NCI NIH HHS K08 CA095152NCI NIH HHS P01 CA059350NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA138738NIAID NIH HHS AI057157NIAID NIH HHS AI56363NIAID NIH HHS U19 AI056363NIAID NIH HHS U54 AI057157
6 · The paper itself

Abstract

Adoptive cell therapy with tumor-targeted T cells is a promising approach to cancer therapy. Enhanced clinical outcome using this approach requires conditioning regimens with total body irradiation, lymphodepleting chemotherapy, and/or additional cytokine support. However, the need for prior conditioning precludes optimal application of this approach to a significant number of cancer patients intolerant to these regimens. Herein, we present preclinical studies demonstrating that treatment with CD19-specific, chimeric antigen receptor (CAR)-modified T cells that are further modified to constitutively secrete IL-12 are able to safely eradicate established disease in the absence of prior conditioning. We demonstrate in a novel syngeneic tumor model that tumor elimination requires both CD4(+) and CD8(+) T-cell subsets, autocrine IL-12 stimulation, and subsequent IFNγ secretion by the CAR(+) T cells. Importantly, IL-12-secreting, tumor-targeted T cells acquire intrinsic resistance to T regulatory cell-mediated inhibition. Based on these preclinical data, we anticipate that adoptive therapy using CAR-targeted T cells modified to secrete IL-12 will obviate or reduce the need for potentially hazardous conditioning regimens to achieve optimal antitumor responses in cancer patients.

Indexed as

Immunotherapy, AdoptiveTransplantation ConditioningAnimalsAntigens, CD19Antineoplastic Agents, AlkylatingB7-1 AntigenB-LymphocytesCombined Modality TherapyCyclophosphamideCytotoxicity, ImmunologicHumansInterferon-gammaInterleukin-12MiceMice, Inbred C57BLMice, KnockoutAntigens, CD19Antineoplastic Agents, AlkylatingB7-1 AntigenCyclophosphamideInterferon-gammaInterleukin-12Recombinant Fusion Proteins

Identifiers

PMID22354001
PMCPMC3359735
OpenAlexW2046562334

What OpenQuestion holds

Textmetadata
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.