PMID- 21915103
OWN - NLM
STAT- MEDLINE
DCOM- 20120322
LR  - 20211020
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 19
IP  - 12
DP  - 2011 Dec
TI  - Cytotoxic T lymphocytes simultaneously targeting multiple tumor-associated 
      antigens to treat EBV negative lymphoma.
PG  - 2258-68
LID - 10.1038/mt.2011.167 [doi]
AB  - Although immunotherapy with Epstein-Barr virus (EBV)-specific cytotoxic T 
      lymphocytes (CTLs) can treat EBV-associated Hodgkin and non-Hodgkin lymphoma 
      (HL/NHL), more than 50% of such tumors are EBV negative. We now describe an 
      approach that allows us to consistently generate, in a single line, CTLs that 
      recognize a wide spectrum of nonviral tumor-associated antigens (TAAs) expressed 
      by human HL/NHL, including Survivin, MAGE-A4, Synovial sarcoma X (SSX2), 
      preferentially expressed antigen in melanoma (PRAME) and NY-ESO-1. We could 
      generate these CTLs from nine of nine healthy donors and five of eight lymphoma 
      patients, irrespective of human leukocyte antigen (HLA) type. We reactivated 
      TAA-directed T cells ex vivo, by stimulation with dendritic cells (DCs) pulsed 
      with overlapping peptide libraries spanning the chosen antigens in the presence 
      of an optimized Th1-polarizing, prosurvival/proliferative and Treg inhibitory 
      cytokine combination. The resultant lines of CD4(+) and CD8(+), 
      polycytokine-producing T cells are directed against a multiplicity of epitopes 
      expressed on the selected TAAs, with cytolytic activity against autologous tumor 
      cells. Infusion of such multispecific monocultures may extend the benefits of CTL 
      therapy to treatment even of EBV negative HL and NHL.
FAU - Gerdemann, Ulrike
AU  - Gerdemann U
AD  - Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist 
      Hospital, Texas Children's Hospital, Houston, Texas 77030, USA.
FAU - Katari, Usha
AU  - Katari U
FAU - Christin, Anne S
AU  - Christin AS
FAU - Cruz, Conrad R
AU  - Cruz CR
FAU - Tripic, Tamara
AU  - Tripic T
FAU - Rousseau, Alexandra
AU  - Rousseau A
FAU - Gottschalk, Stephen M
AU  - Gottschalk SM
FAU - Savoldo, Barbara
AU  - Savoldo B
FAU - Vera, Juan F
AU  - Vera JF
FAU - Heslop, Helen E
AU  - Heslop HE
FAU - Brenner, Malcolm K
AU  - Brenner MK
FAU - Bollard, Catherine M
AU  - Bollard CM
FAU - Rooney, Cliona M
AU  - Rooney CM
FAU - Leen, Ann M
AU  - Leen AM
LA  - eng
GR  - P50 CA126752/CA/NCI NIH HHS/United States
GR  - P50 CA126752-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110913
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Epitopes)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptide Library)
SB  - IM
MH  - Adult
MH  - Antigens, Neoplasm/genetics/*immunology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Epitopes/*immunology
MH  - Epstein-Barr Virus Infections
MH  - Flow Cytometry
MH  - Herpesvirus 4, Human
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - *Immunotherapy
MH  - Lymphocyte Activation
MH  - Lymphoma/*immunology/*therapy
MH  - Monocytes/cytology/immunology/metabolism
MH  - Peptide Fragments/immunology
MH  - Peptide Library
MH  - T-Lymphocytes, Cytotoxic/*immunology
PMC - PMC3242656
EDAT- 2011/09/15 06:00
MHDA- 2012/03/23 06:00
PMCR- 2012/12/01
CRDT- 2011/09/15 06:00
PHST- 2011/09/15 06:00 [entrez]
PHST- 2011/09/15 06:00 [pubmed]
PHST- 2012/03/23 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - S1525-0016(16)32711-3 [pii]
AID - 10.1038/mt.2011.167 [doi]
PST - ppublish
SO  - Mol Ther. 2011 Dec;19(12):2258-68. doi: 10.1038/mt.2011.167. Epub 2011 Sep 13.