PMID- 36452901
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221202
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 9
DP  - 2022
TI  - Safety and durability of AGT103-T autologous T cell therapy for HIV infection in 
      a Phase 1 trial.
PG  - 1044713
LID - 10.3389/fmed.2022.1044713 [doi]
LID - 1044713
AB  - The cell and gene therapy product AGT103-T was designed to restore the 
      Gag-specific CD4+ T cell response in persons with chronic HIV disease who are 
      receiving antiretroviral therapy. This autologous, genetically engineered cell 
      product is under investigation in a Phase 1 clinical trial (NCT03215004). Trial 
      participants were conditioned with cyclophosphamide approximately 1 week before 
      receiving a one-time low (< 10(9) genetically modified CD4+ T cells) or high 
      (>/=10(9) genetically modified CD4+ T cells) dose of AGT103-T, delivering between 2 
      and 21 million genetically modified cells per kilogram (kg) body weight. There 
      were no serious adverse events (SAEs) and all adverse events (AEs) were mild. 
      Genetically modified AGT103-T cells were detected in most of the participant 
      blood samples collected 6 months after infusion, which was the last scheduled 
      monitoring visit. Peripheral blood mononuclear cells (PBMC) collected after cell 
      product infusion were tested to determine the abundance of Gag-specific T cells 
      as a measure of objective responses to therapy. Gag-specific CD4+ T cells were 
      detected in all treated individuals and were substantially increased by 9 to 
      300-fold compared to baseline, by 14 days after cell product infusion. 
      Gag-specific CD8+ T cells were increased by 1.7 to 10-fold relative to baseline, 
      by 28 days after cell product infusion. Levels of Gag-specific CD4+ T cells 
      remained high (~2 to 70-fold higher relative to baseline) throughout 3-6 months 
      after infusion. AGT103-T at low or high doses was safe and effective for 
      improving host T cell immunity to HIV. Further studies, including antiretroviral 
      treatment interruption, are warranted to evaluate the product's efficacy in HIV 
      disease. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: 
      NCT03215004.
CI  - Copyright (c) 2022 Muvarak, Li, Lahusen, Galvin, Kumar, Pauza and Bordon.
FAU - Muvarak, Nidal
AU  - Muvarak N
AD  - American Gene Technologies International, Inc., Rockville, MD, United States.
FAU - Li, Haishan
AU  - Li H
AD  - American Gene Technologies International, Inc., Rockville, MD, United States.
FAU - Lahusen, Tyler
AU  - Lahusen T
AD  - American Gene Technologies International, Inc., Rockville, MD, United States.
FAU - Galvin, Jeffrey A
AU  - Galvin JA
AD  - American Gene Technologies International, Inc., Rockville, MD, United States.
FAU - Kumar, Princy N
AU  - Kumar PN
AD  - Georgetown University School of Medicine, Washington, DC, United States.
FAU - Pauza, C David
AU  - Pauza CD
AD  - American Gene Technologies International, Inc., Rockville, MD, United States.
FAU - Bordon, Jose
AU  - Bordon J
AD  - Washington Health Institute, Washington, DC, United States.
LA  - eng
PT  - Journal Article
DEP - 20221114
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC9701732
OTO - NOTNLM
OT  - HIV
OT  - cell therapy
OT  - functional cure
OT  - gene therapy
OT  - immune reconstitution
COIS- Authors HL, TL, and CP are shareholders in American Gene Technologies 
      International, Inc. Author JG is a shareholder and current employee of American 
      Gene Technologies, International, Inc. Authors PK and JB received funding for 
      clinical trial costs from American Gene Technologies International, Inc. Authors 
      HL and CP are current employees of Viriom Inc. Author NM is a current employee of 
      BioNTech.
EDAT- 2022/12/02 06:00
MHDA- 2022/12/02 06:01
PMCR- 2022/11/14
CRDT- 2022/12/01 02:52
PHST- 2022/09/14 00:00 [received]
PHST- 2022/10/24 00:00 [accepted]
PHST- 2022/12/01 02:52 [entrez]
PHST- 2022/12/02 06:00 [pubmed]
PHST- 2022/12/02 06:01 [medline]
PHST- 2022/11/14 00:00 [pmc-release]
AID - 10.3389/fmed.2022.1044713 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2022 Nov 14;9:1044713. doi: 10.3389/fmed.2022.1044713. 
      eCollection 2022.