Format

Send to

Choose Destination
J Hematol Oncol. 2017 Apr 7;10(1):82. doi: 10.1186/s13045-017-0459-2.

Vaccination with poly(IC:LC) and peptide-pulsed autologous dendritic cells in patients with pancreatic cancer.

Author information

1
Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, 29425, USA. mehrotr@musc.edu.
2
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. mehrotr@musc.edu.
3
Present address: Gibbs Cancer Center and Research Institute, 380 Serpentine Drive, Spartanburg, SC, 29303, USA. mehrotr@musc.edu.
4
Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA.
5
Present address: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
6
Departmet of Population Sciences, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA.
7
Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, 29425, USA.
8
Department of Surgery, Loyola University Medical Center, Maywood, IL, 60153, USA.
9
Center of Excellence in Cancer Research and Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt.
10
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA.
11
Present address: Gibbs Cancer Center and Research Institute, 380 Serpentine Drive, Spartanburg, SC, 29303, USA.
12
Oncovir Inc., 3202 Cleaveland Avenue NW, Washington, DC, 20008, USA.
13
Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, 29425, USA. coledj@musc.edu.
14
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. coledj@musc.edu.

Abstract

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 × 107 peptide-pulsed DC vaccines every 2 weeks (Day 0, 14, 28, and 42). Concurrently, patients received intramuscular administration of Poly-ICLC at 30 μg/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).

PMID:
28388966
PMCID:
PMC5384142
DOI:
10.1186/s13045-017-0459-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center