Evidence map›Paper›PMID 26960932›Full record

ArticleCancer immunology, immunotherapy : CII2016

Systemic delivery of chTNT-3/CpG immunoconjugates for immunotherapy in murine solid tumor models.

Julie K Jang, Leslie A Khawli, David C Canter, Peisheng Hu, Tian H Zhu, Brian W Wu, Trevor E Angell, Zhongjun Li, Alan L Epstein

Open access · greenAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 31% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
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 3 institutions in 2 countries.

Julie K JangDepartment of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 205, Los Angeles, CA, 90033, USA.
Leslie A KhawliDepartment of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 205, Los Angeles, CA, 90033, USA.
David C CanterDepartment of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 205, Los Angeles, CA, 90033, USA.
Peisheng HuDepartment of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 205, Los Angeles, CA, 90033, USA.
Tian H ZhuDepartment of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 205, Los Angeles, CA, 90033, USA.
Brian W WuDepartment of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 205, Los Angeles, CA, 90033, USA.
Trevor E AngellDepartment of Endocrinology, Metabolism, and Hypertension, Thyroid Section, Brigham and Women's Hospital, Boston, MA, USA.
Zhongjun LiDepartment of Blood Transfusion, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Alan L EpsteinDepartment of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 205, Los Angeles, CA, 90033, USA. aepstein@usc.edu.
University of Southern California · USArmy Medical University · CNBrigham and Women's Hospital · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Southern California Clinical and Translational Science InstituteUL1TR000130 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A · 2012 to 2015
$36.0M
Southern California Clinical and Translational Science InstituteTL1TR000132 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A · 2012 to 2014
$491k
NCATS NIH HHS TL1 TR000132NCATS NIH HHS TL1TR000132NCATS NIH HHS UL1TR00013NCATS NIH HHS UL1 TR000130NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089
6 · The paper itself

Abstract

CpG oligodeoxynucleotides (CpG) potently activate the immune system by mimicking microbial DNA. Conjugation of CpG to chTNT-3, an antibody targeting the necrotic centers of tumors, enabled CpG to accumulate in tumors after systemic delivery, where it can activate the immune system in the presence of tumor antigens. CpG chemically conjugated to chTNT-3 (chTNT-3/CpG) were compared to free CpG in their ability to stimulate the immune system in vitro and reduce tumor burden in vivo. In subcutaneous Colon 26 adenocarcinoma and B16-F10 melanoma models in BALB/c and C57BL/6 mice, respectively, chTNT-3/CpG, free CpG, or several different control constructs were administered systemically. Intraperitoneal injections of chTNT-3/CpG delayed tumor growth and improved survival and were comparable to intratumorally administered CpG. Compared to saline-treated mice, chTNT-3/CpG-treated mice had smaller average tumor volumes by as much as 72% in Colon 26-bearing mice and 79% in B16-bearing mice. Systemically delivered free CpG and CpG conjugated to an isotype control antibody did not reduce tumor burden or improve survival. In this study, chTNT-3/CpG retained immunostimulatory activity of the CpG moiety and enabled delivery to tumors. Because systemically administered CpG rapidly clear the body and do not accumulate into tumors, chTNT-3/CpG provide a solution to the limitations observed in preclinical and clinical trials.

Indexed as

AnimalsAntibodies, MonoclonalCell LineCell Line, TumorCytokinesFemaleFlow CytometryHumansImmunoconjugatesImmunotherapyInjections, IntralesionalInjections, IntraperitonealMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalOligodeoxyribonucleotidesAntibodies, MonoclonalCPG-oligonucleotideCytokinesImmunoconjugatesOligodeoxyribonucleotidesRecombinant Fusion ProteinsCpG oligodeoxynucleotidesImmunoconjugateImmunotherapySolid tumorsToll-like receptor agonist

Identifiers

PMID26960932
PMCPMC4841721
OpenAlexW2294193109

What OpenQuestion holds

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LicenceTDM
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.