PMID- 35228263
OWN - NLM
STAT- MEDLINE
DCOM- 20220509
LR  - 20230321
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 208
IP  - 6
DP  - 2022 Mar 15
TI  - Phase I Trial Characterizing the Pharmacokinetic Profile of N-803, a Chimeric 
      IL-15 Superagonist, in Healthy Volunteers.
PG  - 1362-1370
LID - 10.4049/jimmunol.2100066 [doi]
AB  - The oncotherapeutic promise of IL-15, a potent immunostimulant, is limited by a 
      short serum t (1/2) The fusion protein N-803 is a chimeric IL-15 superagonist 
      that has a >20-fold longer in vivo t (1/2) versus IL-15. This phase 1 study 
      characterized the pharmacokinetic (PK) profile and safety of N-803 after s.c. 
      administration to healthy human volunteers. Volunteers received two doses of 
      N-803, and after each dose, PK and safety were assessed for 9 d. The primary 
      endpoint was the N-803 PK profile, the secondary endpoint was safety, and immune 
      cell levels and immunogenicity were measures of interest. Serum N-803 
      concentrations peaked 4 h after administration and declined with a t (1/2) of  approximately 20 
      h. N-803 did not cause treatment-emergent serious adverse events (AEs) or grade 
      >/=3 AEs. Injection site reactions, chills, and pyrexia were the most common AEs. 
      Administration of N-803 was well tolerated and accompanied by proliferation of NK 
      cells and CD8(+) T cells and sustained increases in the number of NK cells. Our 
      results suggest that N-803 administration can potentiate antitumor immunity.
CI  - Copyright (c) 2022 by The American Association of Immunologists, Inc.
FAU - Rubinstein, Mark P
AU  - Rubinstein MP
AD  - The Pelotonia Institute for Immuno-Oncology, The Ohio State University James 
      Comprehensive Cancer Center, Columbus, OH.
AD  - Department of Internal Medicine, The Ohio State University, Columbus, OH.
FAU - Williams, Cameron
AU  - Williams C
AD  - Department of Surgery, Medical University of South Carolina, Charleston, SC.
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC.
FAU - Mart, Caroline
AU  - Mart C
AUID- ORCID: 0000-0002-7526-6909
AD  - Department of Surgery, Medical University of South Carolina, Charleston, SC.
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC.
FAU - Beall, Jonathan
AU  - Beall J
AD  - Department of Public Health Sciences, Medical University of South Carolina, 
      Charleston, SC.
FAU - MacPherson, Linda
AU  - MacPherson L
AD  - Department of Surgery, Medical University of South Carolina, Charleston, SC.
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC.
FAU - Azar, Joseph
AU  - Azar J
AUID- ORCID: 0000-0001-9518-2908
AD  - The Pelotonia Institute for Immuno-Oncology, The Ohio State University James 
      Comprehensive Cancer Center, Columbus, OH.
AD  - Department of Internal Medicine, The Ohio State University, Columbus, OH.
FAU - Swiderska-Syn, Marzena
AU  - Swiderska-Syn M
AD  - Department of Surgery, Medical University of South Carolina, Charleston, SC.
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC.
FAU - Manca, Paolo
AU  - Manca P
AUID- ORCID: 0000-0002-3813-6339
AD  - Department of Medical Oncology, IRCCS Foundation - National Cancer Institute, 
      Milan, Italy.
FAU - Gibney, Barry C
AU  - Gibney BC
AD  - Department of Surgery, Medical University of South Carolina, Charleston, SC.
FAU - Robinson, Mark D
AU  - Robinson MD
AUID- ORCID: 0000-0002-3048-5518
AD  - Department of Molecular Life Sciences and SIB Swiss Institute of Bioinformatics, 
      University of Zurich, Zurich, Switzerland.
FAU - Krieg, Carsten
AU  - Krieg C
AUID- ORCID: 0000-0002-5145-7591
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC.
FAU - Hill, Elizabeth G
AU  - Hill EG
AD  - Department of Public Health Sciences, Medical University of South Carolina, 
      Charleston, SC.
FAU - Taha, Sharif A
AU  - Taha SA
AD  - ImmunityBio, Inc., Culver City, CA; and.
FAU - Rock, Amy D
AU  - Rock AD
AD  - ImmunityBio, Inc., Culver City, CA; and.
FAU - Lee, John H
AU  - Lee JH
AUID- ORCID: 0000-0002-5674-7969
AD  - ImmunityBio, Inc., Culver City, CA; and.
FAU - Soon-Shiong, Patrick
AU  - Soon-Shiong P
AD  - ImmunityBio, Inc., Culver City, CA; and.
FAU - Wrangle, John
AU  - Wrangle J
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC; wrangle@musc.edu.
AD  - Division of Hematology and Oncology, Department of Medicine, Medical University 
      of South Carolina, Charleston, SC.
LA  - eng
GR  - K12 CA157688/CA/NCI NIH HHS/United States
GR  - P30 CA138313/CA/NCI NIH HHS/United States
GR  - R01 CA222817/CA/NCI NIH HHS/United States
GR  - P01 CA154778/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220228
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (ALT-803)
RN  - 0 (Interleukin-15)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - *CD8-Positive T-Lymphocytes
MH  - Healthy Volunteers
MH  - Humans
MH  - *Interleukin-15
MH  - Recombinant Fusion Proteins
EDAT- 2022/03/02 06:00
MHDA- 2022/05/10 06:00
CRDT- 2022/03/01 05:54
PHST- 2021/02/01 00:00 [received]
PHST- 2022/01/03 00:00 [accepted]
PHST- 2022/03/02 06:00 [pubmed]
PHST- 2022/05/10 06:00 [medline]
PHST- 2022/03/01 05:54 [entrez]
AID - jimmunol.2100066 [pii]
AID - 10.4049/jimmunol.2100066 [doi]
PST - ppublish
SO  - J Immunol. 2022 Mar 15;208(6):1362-1370. doi: 10.4049/jimmunol.2100066. Epub 2022 
      Feb 28.