Evidence map›Paper›PMID 31836191›Full record

ReviewTrends in pharmacological sciences2020

Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy.

Yang Liu, Pan Zheng

2 registry-linked trialsAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Trends in pharmacological sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 109 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 4 pooled it
–field-weighted citation impact
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.

NCT04140526 phase1 / phase2active not recruitingnot on this map

Safety, Pharmacokinetics (PK), and Efficacy of ONC-392 as a Single Agent and in Combination With Pembrolizumab in Advanced Solid Tumors and NSCLC: An Open Label Phase IA/IB Study. Preserve CTLA4 Checkpoint Function (PRESERVE-001)

TypeinterventionalSponsorOncoC4, Inc.Ran2020 to 2027Enrolled733ConditionsNon Small Cell Lung Cancer, Advanced Solid Tumor, Metastatic Melanoma, Metastatic Head and Neck CarcinomaArmsONC-392, Pembrolizumab, Docetaxel
NCT05671510 phase3active not recruitingnot on this mapstarted 2023, after this paper: background citation

Phase 3, Two-stage, Randomized Study of ONC-392 Versus Docetaxel in Metastatic Non-Small Cell Lung Cancers That Progressed on PD-1/PD-L1 Inhibitors

TypeinterventionalSponsorOncoC4, Inc.Ran2023 to 2028Enrolled630ConditionsNon Small Cell Lung CancerArmsGotistobart, Docetaxel
3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. B cells in cancer: functions, mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2026
    Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article

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

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

2 authors.

Yang LiuDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland, Baltimore, MD 21201, USA; OncoImmune, Inc., Rockville, MD 20850, USA. Electronic address: yaliu@ihv.umaryland.edu.
Pan ZhengDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland, Baltimore, MD 21201, USA; OncoImmune, Inc., Rockville, MD 20850, USA. Electronic address: pzheng@ihv.umaryland.edu.

Funding

Checkpoints of Host Response to Cellular InjuriesR01AI064350 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIU, YANG, ZHENG, PAN · 2006 to 2019
$5.6M
First in Human Phase I/II clinical trial of ONC-392: Preserving CTLA-4 immune tolerance checkpoint for safer and more effective cancer immunotherapyR44CA250824 · NCI · ONCOIMMUNE, INC. · PI HE, KAI, LI, TIANHONG · 2020 to 2022
$2.4M
A Mouse Model to Assess Long Term Immunotherapy-related Adverse Effects in ChildrenR01CA227671 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI WANG, YIN · 2018 to 2022
$2.1M
NCI NIH HHS R01 CA227671NCI NIH HHS R44 CA250824NIAID NIH HHS R01 AI064350
6 · The paper itself

Abstract

A major paradigm in cancer immunotherapy is the use of checkpoint inhibitors to break regulatory mechanisms that usually guard the host against autoimmune diseases. CTLA-4-targeting immunotherapy was the first example that helped establish this paradigm. However, the clinically tested anti-CTLA-4 antibodies exhibit suboptimal efficacy but high toxicity. Recent studies have demonstrated that immunotherapy-related adverse events (irAE) and the cancer immunotherapeutic effect (CITE) represent distinct and therapeutically separable activities of anti-CTLA-4 antibodies. The former is attributable to inactivation of the CTLA-4 checkpoint, while the latter is due to selective depletion of regulatory T cells (Treg) in a tumor microenvironment. Here we argue that for safer and more effective CTLA-4-targeting immune therapy, one should preserve rather than inhibit the CTLA-4 checkpoint while enhancing the efficacy and selectivity of Treg depletion in a tumor microenvironment.

Indexed as

AnimalsCTLA-4 AntigenHumansImmune Checkpoint InhibitorsMolecular Targeted TherapyNeoplasmsT-Lymphocytes, RegulatoryCTLA-4 AntigenImmune Checkpoint Inhibitorscancer immunotherapycheckpoint blockade immunotherapyCTLA-4immunotherapy-related adverse eventsregulatory T cells

Identifiers

PMID31836191
PMCPMC7210725

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.