PMID- 30249388 OWN - NLM STAT- MEDLINE DCOM- 20190814 LR - 20191023 IS - 1525-0024 (Electronic) IS - 1525-0016 (Print) IS - 1525-0016 (Linking) VI - 26 IP - 10 DP - 2018 Oct 3 TI - HIV-Specific, Ex Vivo Expanded T Cell Therapy: Feasibility, Safety, and Efficacy in ART-Suppressed HIV-Infected Individuals. PG - 2496-2506 LID - S1525-0016(18)30400-3 [pii] LID - 10.1016/j.ymthe.2018.08.015 [doi] AB - Adoptive T cell therapy has had dramatic successes in the treatment of virus-related malignancies and infections following hematopoietic stem cell transplantation. We adapted this method to produce ex vivo expanded HIV-specific T cells (HXTCs), with the long-term goal of using HXTCs as part of strategies to clear persistent HIV infection. In this phase 1 proof-of-concept study (NCT02208167), we administered HXTCs to antiretroviral therapy (ART)-suppressed, HIV-infected participants. Participants received two infusions of 2 x 10(7) cells/m(2) HXTCs at a 2-week interval. Leukapheresis was performed at baseline and 12 weeks post-infusion to measure the frequency of resting cell infection by the quantitative viral outgrowth assay (QVOA). Overall, participants tolerated HXTCs, with only grade 1 adverse events (AEs) related to HXTCs. Two of six participants exhibited a detectable increase in CD8 T cell-mediated antiviral activity following the two infusions in some, but not all, assays. As expected, however, in the absence of a latency reversing agent, no meaningful decline in the frequency of resting CD4 T cell infection was detected. HXTC therapy in ART-suppressed, HIV-infected individuals appears safe and well tolerated, without any clinical signs of immune activation, likely due to the low residual HIV antigen burden present during ART. CI - Copyright (c) 2018. Published by Elsevier Inc. FAU - Sung, Julia A AU - Sung JA AD - UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Patel, Shabnum AU - Patel S AD - Center for Cancer and Immunology Research, Children's National Health System, Washington, DC 20010, USA. FAU - Clohosey, Matthew L AU - Clohosey ML AD - UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Roesch, Lauren AU - Roesch L AD - Center for Cancer and Immunology Research, Children's National Health System, Washington, DC 20010, USA. FAU - Tripic, Tamara AU - Tripic T AD - Section of Hematology-Oncology, Department of Pediatrics, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA. FAU - Kuruc, JoAnn D AU - Kuruc JD AD - UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Archin, Nancie AU - Archin N AD - UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Hanley, Patrick J AU - Hanley PJ AD - Center for Cancer and Immunology Research, Children's National Health System, Washington, DC 20010, USA. FAU - Cruz, C Russell AU - Cruz CR AD - Center for Cancer and Immunology Research, Children's National Health System, Washington, DC 20010, USA. FAU - Goonetilleke, Nilu AU - Goonetilleke N AD - UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Eron, Joseph J AU - Eron JJ AD - UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Rooney, Clio M AU - Rooney CM AD - Section of Hematology-Oncology, Department of Pediatrics, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA. FAU - Gay, Cynthia L AU - Gay CL AD - UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Bollard, Catherine M AU - Bollard CM AD - Center for Cancer and Immunology Research, Children's National Health System, Washington, DC 20010, USA. Electronic address: cbollard@childrensnational.org. FAU - Margolis, David M AU - Margolis DM AD - UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: dmargo@med.unc.edu. LA - eng SI - ClinicalTrials.gov/NCT02208167 GR - R01 HL132791/HL/NHLBI NIH HHS/United States GR - N01HB37163/HL/NHLBI NIH HHS/United States GR - UM1 AI126619/AI/NIAID NIH HHS/United States GR - KL2 TR001109/TR/NCATS NIH HHS/United States GR - P30 CA016086/CA/NCI NIH HHS/United States GR - N01 HB037163/HC/NHLBI NIH HHS/United States GR - P30 AI050410/AI/NIAID 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 - 20180921 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 MH - Adult MH - Aged MH - Antiretroviral Therapy, Highly Active/*methods MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - *Cell- and Tissue-Based Therapy MH - Female MH - Genetic Therapy MH - HIV Infections/genetics/immunology/*therapy/virology MH - HIV-1/immunology/pathogenicity MH - Humans MH - Male MH - Middle Aged MH - T-Lymphocytes/immunology/*transplantation MH - Virus Activation/genetics/immunology MH - Virus Replication/genetics/immunology PMC - PMC6171327 OTO - NOTNLM OT - HIV OT - cell therapy OT - latency EDAT- 2018/09/27 06:00 MHDA- 2019/08/15 06:00 PMCR- 2019/10/03 CRDT- 2018/09/26 06:00 PHST- 2018/04/04 00:00 [received] PHST- 2018/07/19 00:00 [revised] PHST- 2018/08/15 00:00 [accepted] PHST- 2018/09/27 06:00 [pubmed] PHST- 2019/08/15 06:00 [medline] PHST- 2018/09/26 06:00 [entrez] PHST- 2019/10/03 00:00 [pmc-release] AID - S1525-0016(18)30400-3 [pii] AID - 10.1016/j.ymthe.2018.08.015 [doi] PST - ppublish SO - Mol Ther. 2018 Oct 3;26(10):2496-2506. doi: 10.1016/j.ymthe.2018.08.015. Epub 2018 Sep 21.