PMID- 28388966
OWN - NLM
STAT- MEDLINE
DCOM- 20171201
LR  - 20210103
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 10
IP  - 1
DP  - 2017 Apr 7
TI  - Vaccination with poly(IC:LC) and peptide-pulsed autologous dendritic cells in 
      patients with pancreatic cancer.
PG  - 82
LID - 10.1186/s13045-017-0459-2 [doi]
LID - 82
AB  - BACKGROUND: Dendritic cells (DCs) enhance the quality of anti-tumor immune 
      response in patients with cancer. Thus, we posit that DC-based immunotherapy, in 
      conjunction with toll-like receptor (TLR)-3 agonist poly-ICLC, is a promising 
      approach for harnessing immunity against metastatic or locally advanced 
      unresectable pancreatic cancer (PC). METHODS: We generated autologous DCs from 
      the peripheral blood of HLA-A2(+) patients with PC. DCs were pulsed with three 
      distinct A2-restricted peptides: 1) human telomerase reverse transcriptase 
      (hTERT, TERT572Y), 2) carcinoembryonic antigen (CEA; Cap1-6D), and 3) survivin 
      (SRV.A2). Patients received four intradermal injections of 1 x 10(7) 
      peptide-pulsed DC vaccines every 2 weeks (Day 0, 14, 28, and 42). Concurrently, 
      patients received intramuscular administration of Poly-ICLC at 30 mug/Kg on 
      vaccination days (i.e., day 0, 14, 28, and 42), as well as on days 3, 17, 21, 31, 
      37, and 45. Our key objective was to assess safety and feasibility. The effect of 
      DC vaccination on immune response was measured at each DC injection time point by 
      enumerating the phenotype and function of patient T cells. RESULTS: Twelve 
      patients underwent apheresis: nine patients with metastatic disease, and three 
      patients with locally advanced unresectable disease. Vaccines were successfully 
      manufactured from all individuals. We found that this treatment was 
      well-tolerated, with the most common symptoms being fatigue and/or self-limiting 
      flu-like symptoms. Among the eight patients who underwent imaging on day 56, four 
      patients experienced stable disease while four patients had disease progression. 
      The median overall survival was 7.7 months. One patient survived for 28 months 
      post leukapheresis. MHC class I -tetramer analysis before and after vaccination 
      revealed effective generation of antigen-specific T cells in three patients with 
      stable disease. CONCLUSION: Vaccination with peptide-pulsed DCs in combination 
      with poly-ICLC is safe and induces a measurable tumor specific T cell population 
      in patients with advanced PC. TRIAL REGISTRATION: NCT01410968 ; Name of registry: 
      clinicaltrials.gov; Date of registration: 08/04/2011).
FAU - Mehrotra, Shikhar
AU  - Mehrotra S
AD  - Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas 
      Street, Charleston, SC, 29425, USA. mehrotr@musc.edu.
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC, 29425, USA. mehrotr@musc.edu.
AD  - Present address: Gibbs Cancer Center and Research Institute, 380 Serpentine 
      Drive, Spartanburg, SC, 29303, USA. mehrotr@musc.edu.
FAU - Britten, Carolyn D
AU  - Britten CD
AD  - Division of Hematology/Oncology, Department of Medicine, Medical University of 
      South Carolina, Charleston, SC, 29425, USA.
FAU - Chin, Steve
AU  - Chin S
AD  - Division of Hematology/Oncology, Department of Medicine, Medical University of 
      South Carolina, Charleston, SC, 29425, USA.
AD  - Present address: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 
      46285, USA.
FAU - Garrett-Mayer, Elizabeth
AU  - Garrett-Mayer E
AD  - Departmet of Population Sciences, Hollings Cancer Center, Medical University of 
      South Carolina, Charleston, SC, 29425, USA.
FAU - Cloud, Colleen A
AU  - Cloud CA
AD  - Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas 
      Street, Charleston, SC, 29425, USA.
FAU - Li, Mingli
AU  - Li M
AD  - Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas 
      Street, Charleston, SC, 29425, USA.
FAU - Scurti, Gina
AU  - Scurti G
AD  - Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas 
      Street, Charleston, SC, 29425, USA.
AD  - Department of Surgery, Loyola University Medical Center, Maywood, IL, 60153, USA.
FAU - Salem, Mohamed L
AU  - Salem ML
AD  - Center of Excellence in Cancer Research and Zoology Department, Faculty of 
      Science, Tanta University, Tanta, Egypt.
FAU - Nelson, Michelle H
AU  - Nelson MH
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC, 29425, USA.
FAU - Thomas, Melanie B
AU  - Thomas MB
AD  - Division of Hematology/Oncology, Department of Medicine, Medical University of 
      South Carolina, Charleston, SC, 29425, USA.
AD  - Present address: Gibbs Cancer Center and Research Institute, 380 Serpentine 
      Drive, Spartanburg, SC, 29303, USA.
FAU - Paulos, Chrystal M
AU  - Paulos CM
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC, 29425, USA.
FAU - Salazar, Andres M
AU  - Salazar AM
AD  - Oncovir Inc., 3202 Cleaveland Avenue NW, Washington, DC, 20008, USA.
FAU - Nishimura, Michael I
AU  - Nishimura MI
AD  - Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas 
      Street, Charleston, SC, 29425, USA.
AD  - Department of Surgery, Loyola University Medical Center, Maywood, IL, 60153, USA.
FAU - Rubinstein, Mark P
AU  - Rubinstein MP
AD  - Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas 
      Street, Charleston, SC, 29425, USA.
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC, 29425, USA.
FAU - Li, Zihai
AU  - Li Z
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC, 29425, USA.
FAU - Cole, David J
AU  - Cole DJ
AD  - Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas 
      Street, Charleston, SC, 29425, USA. coledj@musc.edu.
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC, 29425, USA. coledj@musc.edu.
LA  - eng
SI  - ClinicalTrials.gov/NCT01410968
GR  - P30 CA138313/CA/NCI NIH HHS/United States
GR  - UL1 TR000062/TR/NCATS NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
DEP - 20170407
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Peptides)
RN  - 25104-18-1 (Polylysine)
RN  - 7KYP9TKT70 (poly ICLC)
RN  - K679OBS311 (Carboxymethylcellulose Sodium)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Aged
MH  - Antigens, Neoplasm/immunology
MH  - Cancer Vaccines/*administration & dosage/pharmacology
MH  - Carboxymethylcellulose Sodium/administration & dosage/*analogs & 
      derivatives/pharmacology
MH  - Dendritic Cells/*immunology/transplantation
MH  - Female
MH  - Humans
MH  - Immunotherapy, Active/methods
MH  - Lymphocyte Activation
MH  - Lymphocyte Count
MH  - Male
MH  - Middle Aged
MH  - Pancreatic Neoplasms/*therapy
MH  - Peptides/immunology
MH  - Pilot Projects
MH  - Poly I-C/*administration & dosage/pharmacology
MH  - Polylysine/administration & dosage/*analogs & derivatives/pharmacology
MH  - Transplantation, Autologous
MH  - Vaccination/*methods
PMC - PMC5384142
EDAT- 2017/04/09 06:00
MHDA- 2017/12/02 06:00
PMCR- 2017/04/07
CRDT- 2017/04/09 06:00
PHST- 2016/12/03 00:00 [received]
PHST- 2017/03/30 00:00 [accepted]
PHST- 2017/04/09 06:00 [entrez]
PHST- 2017/04/09 06:00 [pubmed]
PHST- 2017/12/02 06:00 [medline]
PHST- 2017/04/07 00:00 [pmc-release]
AID - 10.1186/s13045-017-0459-2 [pii]
AID - 459 [pii]
AID - 10.1186/s13045-017-0459-2 [doi]
PST - epublish
SO  - J Hematol Oncol. 2017 Apr 7;10(1):82. doi: 10.1186/s13045-017-0459-2.