PMID- 28783452
OWN - NLM
STAT- MEDLINE
DCOM- 20171030
LR  - 20220410
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 35
IP  - 31
DP  - 2017 Nov 1
TI  - Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, 
      Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic 
      Hematopoietic Stem-Cell Transplantation.
PG  - 3547-3557
LID - 10.1200/JCO.2017.73.0655 [doi]
AB  - Purpose Improvement of cure rates for patients treated with allogeneic 
      hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease 
      treatment-related mortality from severe viral infections. Adoptively transferred 
      virus-specific T cells (VSTs) generated from eligible, third-party donors could 
      provide broad antiviral protection to recipients of HSCT as an immediately 
      available off-the-shelf product. Patient and Methods We generated a bank of VSTs 
      that recognized five common viral pathogens: Epstein-Barr virus (EBV), adenovirus 
      (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6). 
      The VSTs were administered to 38 patients with 45 infections in a phase II 
      clinical trial. Results A single infusion produced a cumulative complete or 
      partial response rate of 92% (95% CI, 78.1% to 98.3%) overall and the following 
      rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7), 
      100% for EBV (n = 2), and 67% for HHV-6 (n = 3). Clinical benefit was achieved in 
      31 patients treated for one infection and in seven patients treated for multiple 
      coincident infections. Thirteen of 14 patients treated for BKV-associated 
      hemorrhagic cystitis experienced complete resolution of gross hematuria by week 
      6. Infusions were safe, and only two occurrences of de novo graft-versus host 
      disease (grade 1) were observed. VST tracking by epitope profiling revealed 
      persistence of functional VSTs of third-party origin for up to 12 weeks. 
      Conclusion The use of banked VSTs is a feasible, safe, and effective approach to 
      treat severe and drug-refractory infections after HSCT, including infections from 
      two viruses (BKV and HHV-6) that had never been targeted previously with an 
      off-the-shelf product. Furthermore, the multispecificity of the VSTs ensures 
      extensive antiviral coverage, which facilitates the treatment of patients with 
      multiple infections.
FAU - Tzannou, Ifigeneia
AU  - Tzannou I
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Papadopoulou, Anastasia
AU  - Papadopoulou A
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Naik, Swati
AU  - Naik S
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Leung, Kathryn
AU  - Leung K
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Martinez, Caridad A
AU  - Martinez CA
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Ramos, Carlos A
AU  - Ramos CA
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Carrum, George
AU  - Carrum G
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Sasa, Ghadir
AU  - Sasa G
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Lulla, Premal
AU  - Lulla P
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Watanabe, Ayumi
AU  - Watanabe A
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Kuvalekar, Manik
AU  - Kuvalekar M
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Gee, Adrian P
AU  - Gee AP
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Wu, Meng-Fen
AU  - Wu MF
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Liu, Hao
AU  - Liu H
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Grilley, Bambi J
AU  - Grilley BJ
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Krance, Robert A
AU  - Krance RA
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Gottschalk, Stephen
AU  - Gottschalk S
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Brenner, Malcolm K
AU  - Brenner MK
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Rooney, Cliona M
AU  - Rooney CM
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Heslop, Helen E
AU  - Heslop HE
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Leen, Ann M
AU  - Leen AM
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
FAU - Omer, Bilal
AU  - Omer B
AD  - Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A. 
      Martinez, Carlos A. Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi 
      Watanabe, Manik Kuvalekar, Adrian P. Gee, Bambi J. Grilley, Robert A. Krance, 
      Stephen Gottschalk, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. 
      Leen, and Bilal Omer, Center for Cell and Gene Therapy, Baylor College of 
      Medicine, Texas Children's Hospital, and Houston Methodist Hospital; Meng-Fen Wu 
      and Hao Liu, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, 
      TX.
LA  - eng
GR  - P50 CA126752/CA/NCI NIH HHS/United States
GR  - P30 CA125123/CA/NCI NIH HHS/United States
GR  - K12 CA090433/CA/NCI NIH HHS/United States
GR  - P01 CA094237/CA/NCI NIH HHS/United States
GR  - T32 DK060445/DK/NIDDK NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20170807
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
SB  - IM
MH  - Adenoviruses, Human/immunology
MH  - Adult
MH  - BK Virus/immunology
MH  - DNA Virus Infections/etiology/*therapy/virology
MH  - DNA Viruses/*immunology
MH  - Female
MH  - Hematopoietic Stem Cell Transplantation/*adverse effects/*methods
MH  - Herpesvirus 4, Human/immunology
MH  - Herpesvirus 6, Human/immunology
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Male
MH  - T-Lymphocytes/*immunology/*transplantation
MH  - Transplantation, Homologous
MH  - Treatment Outcome
PMC - PMC5662844
EDAT- 2017/08/08 06:00
MHDA- 2017/10/31 06:00
PMCR- 2018/11/01
CRDT- 2017/08/08 06:00
PHST- 2017/08/08 06:00 [pubmed]
PHST- 2017/10/31 06:00 [medline]
PHST- 2017/08/08 06:00 [entrez]
PHST- 2018/11/01 00:00 [pmc-release]
AID - 730655 [pii]
AID - 10.1200/JCO.2017.73.0655 [doi]
PST - ppublish
SO  - J Clin Oncol. 2017 Nov 1;35(31):3547-3557. doi: 10.1200/JCO.2017.73.0655. Epub 
      2017 Aug 7.