PMID- 28411378
OWN - NLM
STAT- MEDLINE
DCOM- 20170911
LR  - 20210103
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 123
IP  - 16
DP  - 2017 Aug 15
TI  - Immune responses and long-term disease recurrence status after telomerase-based 
      dendritic cell immunotherapy in patients with acute myeloid leukemia.
PG  - 3061-3072
LID - 10.1002/cncr.30696 [doi]
AB  - BACKGROUND: Telomerase activity in leukemic blasts frequently is increased among 
      patients with high-risk acute myeloid leukemia (AML). In the current study, the 
      authors evaluated the feasibility, safety, immunogenicity, and therapeutic 
      potential of human telomerase reverse transcriptase (hTERT)-expressing autologous 
      dendritic cells (hTERT-DCs) in adult patients with AML. METHODS: hTERT-DCs were 
      produced from patient-specific leukapheresis, electroporated with an 
      mRNA-encoding hTERT and a lysosomal-targeting sequence, and cryopreserved. A 
      total of 22 patients with a median age of 58 years (range, 30-75 years) with 
      intermediate-risk or high-risk AML in first or second complete remission (CR) 
      were enrolled. hTERT-DCs were generated for 24 patients (73%). A median of 17 
      intradermal vaccinations (range, 6-32 intradermal vaccinations) containing 
      1x10(7) cells were administered as 6 weekly injections followed by 6 biweekly 
      injections. A total of 21 patients (16 in first CR, 3 in second CR, and 2 with 
      early disease recurrence) received hTERT-DCs. RESULTS: hTERT-DCs were well 
      tolerated with no severe toxicities reported, with the exception of 1 patient who 
      developed idiopathic thrombocytopenic purpura. Of the 19 patients receiving 
      hTERT-DCs in CR, 11 patients (58%) developed hTERT-specific T-cell responses that 
      primarily were targeted toward hTERT peptides with predicted low human leukocyte 
      antigen (HLA)-binding affinities. With a median follow-up of 52 months, 58% of 
      patients in CR (11 of 19 patients) were free of disease recurrence at the time of 
      their last follow-up visit; 57% of the patients who were aged >/=60 years (4 of 7 
      patients) also were found to be free of disease recurrence at a median follow-up 
      of 54 months. CONCLUSIONS: The generation of hTERT-DCs is feasible and 
      vaccination with hTERT-DCs appears to be safe and may be associated with 
      favorable recurrence-free survival. Cancer 2017;123:3061-72. (c) 2017 American 
      Cancer Society.
CI  - (c) 2017 American Cancer Society.
FAU - Khoury, Hanna J
AU  - Khoury HJ
AUID- ORCID: 0000-0002-8434-3988
AD  - Department of Hematology and Medical Oncology, Emory University School of 
      Medicine, Atlanta, Georgia.
FAU - Collins, Robert H Jr
AU  - Collins RH Jr
AD  - Department of Internal Medicine, University of Texas Southwestern Medical Center 
      at Dallas, Dallas, Texas.
FAU - Blum, William
AU  - Blum W
AD  - Department of Hematology, The Ohio State University, Columbus, Ohio.
FAU - Stiff, Patrick S
AU  - Stiff PS
AD  - Department of Medicine, Loyola University, Maywood, Illinois.
FAU - Elias, Laurence
AU  - Elias L
AD  - Geron Corporation, Menlo Park, California.
FAU - Lebkowski, Jane S
AU  - Lebkowski JS
AD  - Asterias Biotherapeutics Inc, Menlo Park, California.
FAU - Reddy, Anita
AU  - Reddy A
AD  - Geron Corporation, Menlo Park, California.
FAU - Nishimoto, Kevin P
AU  - Nishimoto KP
AD  - Asterias Biotherapeutics Inc, Menlo Park, California.
FAU - Sen, Debasish
AU  - Sen D
AD  - Asterias Biotherapeutics Inc, Menlo Park, California.
FAU - Wirth, Edward D 3rd
AU  - Wirth ED 3rd
AD  - Asterias Biotherapeutics Inc, Menlo Park, California.
FAU - Case, Casey C
AU  - Case CC
AD  - Asterias Biotherapeutics Inc, Menlo Park, California.
FAU - DiPersio, John F
AU  - DiPersio JF
AD  - Department of Oncology, Washington University School of Medicine, St. Louis, 
      Missouri.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20170414
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Cancer Vaccines)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.7.49 (TERT protein, human)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cancer Vaccines/*therapeutic use
MH  - Dendritic Cells/*metabolism
MH  - Disease-Free Survival
MH  - Enzyme-Linked Immunospot Assay
MH  - Feasibility Studies
MH  - Female
MH  - Humans
MH  - Immunotherapy/*methods
MH  - *Leukapheresis
MH  - Leukemia, Myeloid, Acute/immunology/*therapy
MH  - Male
MH  - Middle Aged
MH  - RNA, Messenger
MH  - Remission Induction
MH  - T-Lymphocytes/immunology
MH  - Telomerase/*genetics
OTO - NOTNLM
OT  - T cells
OT  - acute myeloid leukemia (AML)
OT  - dendritic cells
OT  - human telomerase reverse transcriptase (hTERT)
OT  - immunotherapy
OT  - recurrence-free survival
OT  - telomerase
EDAT- 2017/04/16 06:00
MHDA- 2017/09/12 06:00
CRDT- 2017/04/16 06:00
PHST- 2017/02/16 00:00 [received]
PHST- 2017/02/21 00:00 [accepted]
PHST- 2017/04/16 06:00 [pubmed]
PHST- 2017/09/12 06:00 [medline]
PHST- 2017/04/16 06:00 [entrez]
AID - 10.1002/cncr.30696 [doi]
PST - ppublish
SO  - Cancer. 2017 Aug 15;123(16):3061-3072. doi: 10.1002/cncr.30696. Epub 2017 Apr 14.