Evidence map›Paper›PMID 36967480›Full record

ArticleAging cell2023

Immunotherapeutic approach to reduce senescent cells and alleviate senescence-associated secretory phenotype in mice.

Niraj Shrestha, Pallavi Chaturvedi, Xiaoyun Zhu, Michael J Dee, Varghese George, Christopher Janney, Jack O Egan, Bai Liu, Mark Foster, Lynne Marsala and 28 more

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  9. Review
  10. Effect of physical activity in lymphocytes senescence burden in patients with COPD.American journal of physiology. Lung cellular and molecular physiology · 2024
    Article
  11. Review
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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

38 authors at 3 institutions in 1 country.

Niraj ShresthaHCW Biologics Inc., Miramar, Florida, USA.
Pallavi ChaturvediHCW Biologics Inc., Miramar, Florida, USA.
Xiaoyun ZhuHCW Biologics Inc., Miramar, Florida, USA.
Michael J DeeHCW Biologics Inc., Miramar, Florida, USA.
Varghese GeorgeHCW Biologics Inc., Miramar, Florida, USA.
Christopher JanneyHCW Biologics Inc., Miramar, Florida, USA.
Jack O EganHCW Biologics Inc., Miramar, Florida, USA.
Bai LiuHCW Biologics Inc., Miramar, Florida, USA.
Mark FosterDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
Lynne MarsalaDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
Pamela WongDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
Celia C CubittDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
Jennifer A FoltzDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
Jennifer TranDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
Timothy SchappeDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
Karin HsiaoDepartment of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, Florida, USA.
Gilles M LeclercHCW Biologics Inc., Miramar, Florida, USA.
Lijing YouHCW Biologics Inc., Miramar, Florida, USA.
Christian EcheverriHCW Biologics Inc., Miramar, Florida, USA.
Catherine SpanoudisHCW Biologics Inc., Miramar, Florida, USA.
Ana CarvalhoHCW Biologics Inc., Miramar, Florida, USA.
Leah KanakarajHCW Biologics Inc., Miramar, Florida, USA.
Crystal GilkesHCW Biologics Inc., Miramar, Florida, USA.
Nicole EncaladaHCW Biologics Inc., Miramar, Florida, USA.
Lin KongHCW Biologics Inc., Miramar, Florida, USA.
Meng WangHCW Biologics Inc., Miramar, Florida, USA.
Byron FangHCW Biologics Inc., Miramar, Florida, USA.
Zheng WangHCW Biologics Inc., Miramar, Florida, USA.
Jin-An JiaoHCW Biologics Inc., Miramar, Florida, USA.
Gabriela J MunizHCW Biologics Inc., Miramar, Florida, USA.
Emily K JengHCW Biologics Inc., Miramar, Florida, USA.
Nicole ValdiviesoHCW Biologics Inc., Miramar, Florida, USA.
Liying LiHCW Biologics Inc., Miramar, Florida, USA.
Richard DethDepartment of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, Florida, USA.
Melissa M Berrien-ElliottDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
Todd A FehnigerDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID 0000-0002-8705-2887
Peter R RhodeHCW Biologics Inc., Miramar, Florida, USA.ORCID 0000-0002-4067-4021
Hing C WongHCW Biologics Inc., Miramar, Florida, USA.ORCID 0000-0002-6865-4313
Heat Biologics (United States) · USWashington University in St. Louis · USNova Southeastern University · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI David G DeNardo · 2001 to 2026
$128.0M
Targeting the Bone Marrow Microenvironment In Acute Lymphocytic LeukemiaP50CA171963 · NCI · WASHINGTON UNIVERSITY · PI Daniel C Link · 2013 to 2026
$31.6M
PRE-AND POSTGRADUATE TRAINING IN MOLECULAR HEMATOLOGYT32HL007088 · NHLBI · WASHINGTON UNIVERSITY · PI Grant Anthony Challen, Stephen Oh · 1985 to 2026
$14.1M
Washington University Paul Calabresi K12 Career Development Award for Clinical OncologyK12CA167540 · NCI · WASHINGTON UNIVERSITY · PI John F. Dipersio, Ramaswamy Govindan · 2012 to 2026
$11.7M
TRANSLATING NK CELL BIOLOGY INTO CLINICAL CANCER IMMUNOTHERAPYR01CA205239 · NCI · WASHINGTON UNIVERSITY · PI FEHNIGER, TODD A · 2017 to 2020
$2.4M
Postdoctoral Training Program in Genomic MedicineT32GM139799 · NIGMS · WASHINGTON UNIVERSITY · PI DICKSON, PATRICIA I · 2021 to 2025
$817k
Mechanism of CD8 regulation of natural killer cell biologyF30AI161318 · NIAID · WASHINGTON UNIVERSITY · PI CUBITT, CELIA CLAIRE · 2021 to 2024
$152k
Elucidating the role of EOMES in Memory-Like NK cell DifferentiationF31GM146361 · NIGMS · WASHINGTON UNIVERSITY · PI TRAN, JENNIFER · 2022 to 2024
$90k
NCI NIH HHS K12 CA167540NCI NIH HHS P30 CA091842NCI NIH HHS P50 CA171963NCI NIH HHS R01 CA205239NHLBI NIH HHS T32 HL007088NIAID NIH HHS F30 AI161318NIGMS NIH HHS F31 GM146361NIGMS NIH HHS T32 GM139799
6 · The paper itself

Abstract

Accumulation of senescent cells (SNCs) with a senescence-associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF-β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and SASP, leading to lower expression of pro-inflammatory genes in peripheral organs. HCW9218 treatment also reverted the pattern of key regulatory circadian gene expression in aged mice to levels observed in young mice and impacted genes associated with metabolism and fibrosis in the liver. Single-nucleus RNA Sequencing analysis further revealed that HCW9218 treatment differentially changed the transcriptomic landscape of hepatocyte subtypes involving metabolic, signaling, cell-cycle, and senescence-associated pathways in naturally aged mice. Long-term survival studies also showed that HCW9218 treatment improved physical performance without compromising the health span of naturally aged mice. Thus, HCW9218 represents a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic agents targeting cellular senescence-associated diseases.

Indexed as

Cellular SenescenceSenescence-Associated Secretory PhenotypeAgingAnimalsImmunotherapyInflammationMicePhenotypeagingcellular immunologycircadian genesimmunotherapyinflammationphysical performancesenescencesenescent cell reductionsenomorphictype 2 diabetes

Identifiers

PMID36967480
PMCPMC10186597
OpenAlexW4360985414

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.