ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2015
Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer.
2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase I
In one paragraph
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015. 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 465 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
465citing papers in PubMed, 3 pooled it
17.8field-weighted citation impact, top 1% of its field
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.
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.
Phase I Study of Recombinant Interleukin 15 in Combination With Checkpoint Inhibitors Nivolumab and Ipilimumab in Subjects With Refractory Cancers
First-in-human (FIH), Open-Label, Phase 1a (Dose Escalation)/Phase 1b (Expansion Cohort) Trial of BJ-001 as a Single Agent and in Combination With Pembrolizumab in Patients With Locally Advanced/Metastatic Solid Tumors
Who cites it
465 citing papers in PubMed, 3 syntheses or guidelines pooled it, 691 citations in OpenAlex.
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- Low skeletal muscle mass predicts treatment response in oncology: a meta-analysis.European radiology · 2023Pooled it
- Neoadjuvant immunochemotherapy plus thymalfasin in locally advanced gastric cancer: a prospective clinical trial.BMC medicine · 2026Trial
- A phase 1 study of interleukin-15 in combination with mogamulizumab in relapsed and refractory T-cell malignancies.Blood neoplasia · 2025Trial
- Phase 2 trial (NCI-COTC030) of adjuvant inhaled recombinant human IL-15 combined with amputation and adjuvant chemotherapy in dogs with appendicular osteosarcoma.Frontiers in immunology · 2025Trial
- N-803, an IL-15 Superagonist Complex as Maintenance Therapy After Allogeneic Donor Stem Cell Transplant for Acute Myeloid Leukemia or Myelodysplastic Syndrome; A Phase 2 Trial.Transplantation and cellular therapy · 2024Trial
- Skeletal muscle quality predicts overall survival in advanced liver hepatocellular carcinoma treated with SIRT and sorafenib: A subanalysis of the SORAMIC trial.United European gastroenterology journal · 2024Trial
- Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial.Journal of cachexia, sarcopenia and muscle · 2024Trial
- Prognostic role of radiomics-based body composition analysis for the 1-year survival for hepatocellular carcinoma patients.Journal of cachexia, sarcopenia and muscle · 2023Trial
- αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity by restoring tumor-infiltrating T cells.Cellular & molecular immunology · 2026Article
- The evolving role of cytokines for CAR-T cell manufacturing and beyond.Nature biomedical engineering · 2026Review
- Article
- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- PEG-RLI: A Long-Acting IL-15 Agonist That Produces Massive Levels of CD8Pharmaceutics · 2026Article
- Circumventing Ewing sarcoma tumor microenvironment resistance by IL1RAP CAR-modified TGFβ1-imprinted natural killer cells in combination with IL-15 agonist and anti-GD2 antibody.Journal for immunotherapy of cancer · 2026Article
- Synergistic Oncolytic Effect of HSVtk- and IL-15Rα-Armed Vaccinia Viruses Inducing Systemic Antitumor Immunity.International journal of molecular sciences · 2026Article
- Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Associations Between Body Composition and Intratumoural Immune Cells in Patients With Uterine Cervical Cancer.Journal of cachexia, sarcopenia and muscle · 2026Article
- The Association Between Inflammatory Scores and Frailty Severity: An Exploratory Retrospective Analysis in Non-Small-Cell Lung Cancer Surgical Patients.Medical sciences (Basel, Switzerland) · 2026Article
405 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 1 institution in 1 country.
Kevin C ConlonKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Enrico LugliKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Hugh C WellesKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Steven A RosenbergKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Antonio Tito FojoKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
John C MorrisKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Thomas A FleisherKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Sigrid P DuboisKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Liyanage P PereraKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Donn M StewartKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Carolyn K GoldmanKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Bonita R BryantKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Jean M DeckerKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Jing ChenKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Tat'Yana A WorthyKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
William D FiggKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Cody J PeerKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Michael C SnellerKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
H Clifford LaneKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Jason L YovandichKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Stephen P CreekmoreKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Mario RoedererKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC.
Thomas A WaldmannKevin C. Conlon, Steven A. Rosenberg, Antonio Tito Fojo, John C. Morris, Thomas A. Fleisher, Sigrid P. Dubois, Liyanage P. Perera, Donn M. Stewart, Carolyn K. Goldman, Bonita R. Bryant, Jean M. Decker, Jing Chen, Tat'Yana A. Worthy, William D. Figg Sr, Cody J. Peer, and Thomas A. Waldmann, National Cancer Institute; Enrico Lugli, Hugh C. Welles, Michael C. Sneller, H. Clifford Lane, and Mario Roederer, National Institute of Allergy and Infectious Diseases, Bethesda; Jason L. Yovandich and Stephen P. Creekmore, National Cancer Institute, Frederick, MD; and Hugh C. Welles, Columbian College of Arts and Sciences, George Washington University, Washington, DC. tawald@helix.nih.gov.
George Washington University · US
Funding
Adoptive Cell Transfer Immunotherapy of CancerZIABC010984 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROSENBERG, STEVEN · 2009 to 2025
$56.8MInterleukin-15 Production for Treatment of Patients with Metastatic MalignancyZIBBC010906 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WALDMANN, THOMAS · 2009 to 2022
$29.3MPathogenesis and Treatment of HIV InfectionZIAAI000585 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LANE, CLIFFORD · 2009 to 2025
$26.8MFunctional And Phenotypic Characterization Of T Cells In ManZIAAI005021 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ROEDERER, MARIO · 2009 to 2022
$14.4MIntramural NIH HHS
Abstract
purposeInterleukin-15 (IL-15) has significant potential in cancer immunotherapy as an activator of antitumor CD8 T and natural killer (NK) cells. The primary objectives of this trial were to determine safety, adverse event profile, dose-limiting toxicity, and maximum-tolerated dose of recombinant human IL-15 (rhIL-15) administered as a daily intravenous bolus infusion for 12 consecutive days in patients with metastatic malignancy. PATIENTS AND
methodsWe performed a first in-human trial of Escherichia coli-produced rhIL-15. Bolus infusions of 3.0, 1.0, and 0.3 μg/kg per day of IL-15 were administered for 12 consecutive days to patients with metastatic malignant melanoma or metastatic renal cell cancer.
resultsFlow cytometry of peripheral blood lymphocytes revealed dramatic efflux of NK and memory CD8 T cells from the circulating blood within minutes of IL-15 administration, followed by influx and hyperproliferation yielding 10-fold expansions of NK cells that ultimately returned to baseline. Up to 50-fold increases of serum levels of multiple inflammatory cytokines were observed. Dose-limiting toxicities observed in patients receiving 3.0 and 1.0 μg/kg per day were grade 3 hypotension, thrombocytopenia, and elevations of ALT and AST, resulting in 0.3 μg/kg per day being determined the maximum-tolerated dose. Indications of activity included clearance of lung lesions in two patients.
conclusionIL-15 could be safely administered to patients with metastatic malignancy. IL-15 administration markedly altered homeostasis of lymphocyte subsets in blood, with NK cells and γδ cells most dramatically affected, followed by CD8 memory T cells. To reduce toxicity and increase efficacy, alternative dosing strategies have been initiated, including continuous intravenous infusions and subcutaneous IL-15 administration.
Indexed as
AdultAgedAged, 80 and overArea Under CurveCD4-Positive T-LymphocytesCell ProliferationDose-Response Relationship, DrugDrug Administration ScheduleFemaleFeverHumansInfusions, IntravenousInterleukin-15Killer Cells, NaturalLymphocyte ActivationMaleIL15 protein, humanInterleukin-15Recombinant Proteins
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Registered trials
NCT03388632ClinicalTrials.gov
NCT04294576ClinicalTrials.gov
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.