Evidence map›Paper›PMID 41423270›Full record

ArticleJournal for immunotherapy of cancer2025

TGF-βRII/IL-15 immunotherapeutic complex targets exhausted CD8

Varghese K George, Hing C Wong, Martin Felices, Mark P Rubinstein, Niraj Shrestha, Natalia Valderrama, Hamidreza Farzaneh, Lin Kong, Crystal Gilkes, Alyssa Thompson and 27 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–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.

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

4 citing papers in PubMed.

  1. Article
  2. Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026
    Review
  3. Targeting innate immunity to overcome immune evasion in HPV-associated cancers.Frontiers in cellular and infection microbiology · 2026
    Review
  4. TGF-βRII/IL-15 immunotherapeutic complex targets exhausted CD8Journal for immunotherapy of cancer · 2025
    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

37 authors.

Varghese K GeorgeHCW Biologics Inc, Miramar, Florida, USA.
Hing C WongHCW Biologics Inc, Miramar, Florida, USA.ORCID http://orcid.org/0000-0003-3455-7619
Martin FelicesDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.ORCID http://orcid.org/0000-0002-5945-0634
Mark P RubinsteinDepartment of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
Niraj ShresthaHCW Biologics Inc, Miramar, Florida, USA.ORCID http://orcid.org/0000-0003-3115-6940
Natalia ValderramaHCW Biologics Inc, Miramar, Florida, USA.
Hamidreza FarzanehHCW Biologics Inc, Miramar, Florida, USA.
Lin KongHCW Biologics Inc, Miramar, Florida, USA.
Crystal GilkesHCW Biologics Inc, Miramar, Florida, USA.ORCID http://orcid.org/0009-0008-0984-7132
Alyssa ThompsonHCW Biologics Inc, Miramar, Florida, USA.
Megan LarsonDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.ORCID http://orcid.org/0009-0008-5768-6708
Bai LiuHCW Biologics Inc, Miramar, Florida, USA.
Xiaoyun ZhuHCW Biologics Inc, Miramar, Florida, USA.
Gilles Michel LeclercHCW Biologics Inc, Miramar, Florida, USA.ORCID http://orcid.org/0000-0002-3424-9256
Dongjun ChungPelotonia Institute for Immuno-Oncology, Arthur G James Cancer Hospital and Richard J Solove Research Institute, Columbus, Ohio, USA.ORCID http://orcid.org/0000-0002-8072-5671
Juan XieDivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Jordan KrullDepartment of Biomedical Informatics, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Lucas GomezHCW Biologics Inc, Miramar, Florida, USA.
Leah KanakarajHCW Biologics Inc, Miramar, Florida, USA.ORCID http://orcid.org/0000-0002-4929-6653
Ann BialikUniversity of Miami Leonard M Miller School of Medicine, Miami, Florida, USA.ORCID http://orcid.org/0000-0002-1762-6347
Jack O EganHCW Biologics Inc, Miramar, Florida, USA.ORCID http://orcid.org/0000-0002-8230-5523
Lijing YouHCW Biologics Inc, Miramar, Florida, USA.ORCID http://orcid.org/0009-0009-1511-9286
Xianglan LiuDivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.ORCID http://orcid.org/0009-0006-4308-6598
Rachael TeodorescuDivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Ana K Karen GutierrezThe Ohio State University, Columbus, Ohio, USA.ORCID http://orcid.org/0009-0003-7005-117X
Christian EcheverriHCW Biologics Inc, Miramar, Florida, USA.
Reynier RodriguezHCW Biologics Inc, Miramar, Florida, USA.
Zheng WangHCW Biologics Inc, Miramar, Florida, USA.
Jilan XingHCW Biologics Inc, Miramar, Florida, USA.
Neicy GonzalezHCW Biologics Inc, Miramar, Florida, USA.ORCID http://orcid.org/0009-0009-2180-2153
Pallavi ChaturvediHCW Biologics Inc, Miramar, Florida, USA.
Manish R PatelDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.ORCID http://orcid.org/0000-0003-2752-945X
Rose WangenObstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota, USA.ORCID http://orcid.org/0009-0000-5140-4839
Qing CaoUniversity of Minnesota System, Minneapolis, Minnesota, USA.ORCID http://orcid.org/0000-0002-1523-8797
Peter R RhodeHCW Biologics Inc, Miramar, Florida, USA.ORCID http://orcid.org/0000-0002-4067-4021
Jeffrey S MillerDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Melissa A GellerObstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, Minnesota, USA gelle005@umn.edu.ORCID http://orcid.org/0000-0003-4591-620X

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
Therapeutic Potential of Adaptive NK Cells in Cancer and TransplantationP01CA111412 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MILLER, JEFFREY S. · 2005 to 2025
$38.2M
Targeting off-the-shelf iPSC-derived natural killer cells against solid tumorsR35CA283892 · NCI · UNIVERSITY OF MINNESOTA · PI Jeffrey S. Miller · 2023 to 2026
$3.7M
NCI NIH HHS P01 CA065493NCI NIH HHS P01 CA111412NCI NIH HHS P30 CA077598NCI NIH HHS R35 CA283892
6 · The paper itself

Abstract

backgroundStem-like progenitor exhausted CD8

methodsWe developed a bifunctional TGF-βRII/IL-15 protein complex (HCW9218) and evaluated its antitumor activity in two murine models of melanoma and breast cancer. Peripheral blood, TDLN and tumor-infiltrating CD8

resultsHCW9218 was capable of localizing to the TDLNs and tumors after s.c. administration, neutralized TGF-β, expanded T

conclusionsOur findings demonstrate that combination therapy targeting immune cells critical for antitumor responses and blocking immune-suppressive environment significantly improves antitumor therapeutic efficacy. These findings provide a strong basis for using HCW9218 to enhance the efficacy of ICIs against solid tumors in the clinical setting.

Indexed as

Breast NeoplasmsCD8-Positive T-LymphocytesImmunotherapyInterleukin-15Lymph NodesReceptor, Transforming Growth Factor-beta Type IIAnimalsFemaleHumansMiceTumor MicroenvironmentInterleukin-15Receptor, Transforming Growth Factor-beta Type IIImmune Checkpoint InhibitorImmunotherapyOvarian CancerT cell

Identifiers

PMID41423270
PMCPMC12719900

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.