Evidence map›Paper›PMID 39903538›Full record

ArticleJCI insight2025

Interim report on engineered NK cell trial in lung cancer refractory to immune checkpoint inhibitors.

Miguel A Villalona-Calero, Lei Tian, Xiaochen Li, Joycelynne M Palmer, Claudia Aceves, Hans Meisen, Catherine Cortez, Timothy W Synold, Colt Egelston, Jeffrey VanDeusen and 7 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05334329 (Phase 1 Trial of Umbilical Cord Blood Natural Killer Cells), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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.

NCT05334329 phase1active not recruitingnot on this map

Phase 1 Trial of Umbilical Cord Blood Natural Killer Cells (CB-NK) Expressing Soluble IL-15 (sIL-15) and PD-L1 +/- Atezolizumab in Non-Small Cell Lung Cancer Patients Refractory to PD-1/PD-L1 Immune Checkpoint Inhibitors

TypeinterventionalSponsorUniversity of California, IrvineRan2022 to 2027Enrolled6ConditionsAdvanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Refractory Lung Non-Small Cell CarcinomaArmsAntineoplastic Immune Cell, Atezolizumab, Biospecimen Collection, Cyclophosphamide, Fludarabine
3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. Current and future immunotherapies for NSCLC.Journal of hematology & oncology · 2026
    Review
  3. Review
  4. Nanovaccines for lung cancer: Platforms, mechanistic insights, and translational challenges.Chinese medical journal pulmonary and critical care medicine · 2026
    Review
  5. Review
  6. Review
  7. Article
  8. Natural killer cell-based immunotherapy for cancer.Journal of immunology (Baltimore, Md. : 1950) · 2025
    Review
  9. Review
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

17 authors.

Miguel A Villalona-CaleroThe Department of Medical Oncology and Experimental Therapeutics, Beckman Research Institute and Comprehensive Cancer Center.
Lei TianHematologic Malignancies Research Institute, Department of Hematology and Hematopoietic Stem Cell Transplantation.
Xiaochen LiDivision of Biostatistics, Department of Computational and Quantitative Medicine.
Joycelynne M PalmerHematologic Malignancies Research Institute, Department of Hematology and Hematopoietic Stem Cell Transplantation.
Claudia AcevesBeckman Research Institute, City of Hope National Medical Center, Los Angeles, California, USA.
Hans MeisenBeckman Research Institute, City of Hope National Medical Center, Los Angeles, California, USA.
Catherine CortezBeckman Research Institute, City of Hope National Medical Center, Los Angeles, California, USA.
Timothy W SynoldBeckman Research Institute, City of Hope National Medical Center, Los Angeles, California, USA.
Colt EgelstonBeckman Research Institute, City of Hope National Medical Center, Los Angeles, California, USA.
Jeffrey VanDeusenAvita Health System, Galion, Ohio, USA.
Ivone BrunoCytoImmune Therapeutics, Los Angeles, California, USA.
Lei ZhangCytoImmune Therapeutics, Los Angeles, California, USA.
Eliezer Romeu-BonillaCytoImmune Therapeutics, Los Angeles, California, USA.
Omer ButtCytoImmune Therapeutics, Los Angeles, California, USA.
Stephen J FormanHematologic Malignancies Research Institute, Department of Hematology and Hematopoietic Stem Cell Transplantation.
Michael A CaligiuriHematologic Malignancies Research Institute, Department of Hematology and Hematopoietic Stem Cell Transplantation.
Jianhua YuHematologic Malignancies Research Institute, Department of Hematology and Hematopoietic Stem Cell Transplantation.

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI John Charles Williams · 1985 to 2026
$86.3M
Human natural killer cells: Advancing biology and clinical applicationsR35CA210087 · NCI · OHIO STATE UNIVERSITY · PI MICHAEL A CALIGIURI · 2017 to 2026
$8.3M
Targeting FLT3 for the Treatment of Relapsed or Refractory Acute Myeloid LeukemiaR01CA265095 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI BUDDE, LIHUA ELIZABETH, CALIGIURI, MICHAEL A · 2021 to 2025
$2.4M
Phase 1 Evaluation of Enhanced Natural Killer Cells as a Treatment Strategy in Non-Small cell Lung Cancer Patients Refractory to PD-1/PD-L1 Immune Checkpoint InhibitorsR01CA266457 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI VILLALONA, MIGUEL A, YU, JIANHUA · 2022 to 2025
$1.8M
NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA265095NCI NIH HHS R01 CA266457NCI NIH HHS R35 CA210087
6 · The paper itself

Abstract

backgroundNon-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality, necessitating the exploration of alternate therapeutic approaches. Tumor-reactive or activated-by-cytokine killers (TRACK) are PD-L1+, highly cytolytic NK cells derived from umbilical cord blood NK cells and engineered to express soluble IL-15 (sIL15), and these cells show promise in preclinical studies against NSCLC.

methodsWe assessed safety, persistence, homing, and cytotoxic activity in 6 patients with advanced, refractory, and progressing NSCLC who received a low dose of unmatched, allogeneic, off-the-shelf sIL15_TRACK NK cells. We evaluated NK cell presence and persistence with droplet digital PCR (ddPCR), flow cytometry, and immunofluorescence staining.

resultssIL15_TRACK NK cells had peak measurements at 1 hour and became undetectable 4 hours after each infusion. Cognate ligands to activating NK cell receptors were found in NSCLC. sIL15_TRACK NK cells were observed in a lung tumor biopsy 7 days after the final infusion, confirming their sustainment and tumor-homing ability. They retained cytolytic function following isolation from the lung tumor. Three of 6 patients achieved disease stabilization on repeat imaging, while the others progressed.

conclusionUnmatched, allogeneic, cryopreserved, off-the-shelf sIL15_TRACK NK cells express activating receptors, home to tumor sites that express their cognate ligands, and retain cytolytic activity after infusion, underscoring their potential as a therapeutic approach in solid tumors. At low doses, the therapy was safely administered and showed preliminary evidence of activity in 3 of 6 patients with advanced and progressive NSCLC. Additional dose escalation cohorts and coadministration with atezolizumab are planned.

trial registrationCLINICALTRIALS: gov NCT05334329.

fundingFunding was provided by CytoImmune Therapeutics and grants from the National Cancer Institute (CA266457, CA033572, and CA210087).

Indexed as

Carcinoma, Non-Small-Cell LungInterleukin-15Killer Cells, NaturalLung NeoplasmsAgedFemaleHumansImmune Checkpoint InhibitorsMaleMiddle AgedTreatment OutcomeIL15 protein, humanImmune Checkpoint InhibitorsInterleukin-15Clinical trialsInnate immunityLung cancerNK cellsOncology

Identifiers

PMID39903538
PMCPMC11949060

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.