Evidence map›Paper›PMID 31462678›Full record

ArticleNature communications2019

A next-generation tumor-targeting IL-2 preferentially promotes tumor-infiltrating CD8

Zhichen Sun, Zhenhua Ren, Kaiting Yang, Zhida Liu, Shuaishuai Cao, Sisi Deng, Lily Xu, Yong Liang, Jingya Guo, Yingjie Bian and 5 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 145 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 1 pooled it
9.3field-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

145 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.

  1. Pooled it
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  11. Frontiers in immunology · 2026
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  17. Nanobody-engineered bispecific IL-18 mimetics drive antitumor immunity by engaging CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  18. Review
  19. Article
  20. Review

85 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Zhichen SunKey Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.ORCID http://orcid.org/0000-0001-7837-8407
Zhenhua RenDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235-9072, USA.ORCID http://orcid.org/0000-0002-2560-5618
Kaiting YangKey Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Zhida LiuDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235-9072, USA.ORCID http://orcid.org/0000-0002-3980-8440
Shuaishuai CaoKey Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Sisi DengUniversity of Chinese Academy of Sciences, Beijing, 100049, China.
Lily XuDepartment of Biological Sciences, University of Wellesley College, Wellesley, 02481, MA, USA.
Yong LiangKey Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Jingya GuoKey Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Yingjie BianKey Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.ORCID http://orcid.org/0000-0002-9599-9907
Hairong XuKey Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Jiyun ShiKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Fan WangKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Yang-Xin FuDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235-9072, USA. yang-xin.fu@utsouthwestern.edu.ORCID http://orcid.org/0000-0002-4809-825X
Hua PengKey Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. hpeng@moon.ibp.ac.cn.ORCID http://orcid.org/0000-0002-2482-5475
Chinese Academy of Sciences · CNThe University of Texas Southwestern Medical Center · USSouthwestern Medical Center · USUniversity of Chinese Academy of Sciences · CNWellesley College · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While IL-2 can potently activate both NK and T cells, its short in vivo half-life, severe toxicity, and propensity to amplify Treg cells are major barriers that prevent IL-2 from being widely used for cancer therapy. In this study, we construct a recombinant IL-2 immunocytokine comprising a tumor-targeting antibody (Ab) and a super mutant IL-2 (sumIL-2) with decreased CD25 binding and increased CD122 binding. The Ab-sumIL2 significantly enhances antitumor activity through tumor targeting and specific binding to cytotoxic T lymphocytes (CTLs). We also observe that pre-existing CTLs within the tumor are sufficient and essential for sumIL-2 therapy. This next-generation IL-2 can also overcome targeted therapy-associated resistance. In addition, preoperative sumIL-2 treatment extends survival much longer than standard adjuvant therapy. Finally, Ab-sumIL2 overcomes resistance to immune checkpoint blockade through concurrent immunotherapies. Therefore, this next-generation IL-2 reduces toxicity while increasing TILs that potentiate combined cancer therapies.

Indexed as

AnimalsAntineoplastic Agents, ImmunologicalB7-H1 AntigenCell Line, TumorCetuximabDisease Models, AnimalDrug Resistance, NeoplasmDrug Screening Assays, AntitumorDrug SynergismErb-b2 Receptor Tyrosine KinasesHumansImmunoconjugatesInterleukin-2Interleukin-2 Receptor alpha SubunitInterleukin-2 Receptor beta SubunitLymphocytes, Tumor-InfiltratingAntineoplastic Agents, ImmunologicalB7-H1 AntigenCD274 protein, humanCetuximabERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesIL2 protein, humanIL2RA protein, humanIL2RB protein, humanImmunoconjugatesInterleukin-2Interleukin-2 Receptor alpha SubunitInterleukin-2 Receptor beta SubunitRecombinant Proteins

Identifiers

PMID31462678
PMCPMC6713724
OpenAlexW2971050087

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.