Phase I/II study of GM-CSF DNA as an adjuvant for a multipeptide cancer vaccine in patients with advanced melanoma Journal Article

Authors: Perales, M. A.; Yuan, J.; Powel, S.; Gallardo, H. F.; Rasalan, T. S.; Gonzalez, C.; Manukian, G.; Wang, J.; Zhang, Y.; Chapman, P. B.; Krown, S. E.; Livingston, P. O.; Ejadi, S.; Panageas, K. S.; Engelhorn, M. E.; Terzulli, S. L.; Houghton, A. N.; Wolchok, J. D.
Article Title: Phase I/II study of GM-CSF DNA as an adjuvant for a multipeptide cancer vaccine in patients with advanced melanoma
Abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances immune responses by inducing proliferation, maturation, and migration of dendritic cells (DCs) as well as expansion and differentiation of B and T lymphocytes. The potency of DNA vaccines can be enhanced by the addition of DNA encoding cytokines, acting as molecular adjuvants. We conducted a phase I/II trial of human GM-CSF DNA in conjunction with a multipeptide vaccine (gp100 and tyrosinase) in stage III/IV melanoma patients. Nineteen human leukocyte antigen (HLA)-A*0201(+) patients were treated. Three dose levels were studied: 100, 400, and 800 μg DNA/injection, administered subcutaneously every month with 500 μg of each peptide. In the dose-ranging study, three patients were treated at each dose level. The remaining patients were then treated at the highest dose. Most toxicities were grade 1 injection-site reactions. Eight patients (42%) developed CD8+ T-cell responses, defined by a ≥3 SD increase in baseline reactivity to tyrosinase or gp100 peptide in tetramer or intracellular cytokine staining (ICS) assays. There was no relationship between dose and T-cell response. Responding T cells had an effector memory cell phenotype. Polyfunctional T cells were also demonstrated. At a median of 31 months follow-up, median survival has not been reached. Human GM-CSF DNA was found to be a safe adjuvant.
Keywords: controlled study; clinical trial; interferon; cancer patient; cancer staging; drug megadose; follow up; neoplasm staging; cd8+ t lymphocyte; cell proliferation; lymphocyte proliferation; t lymphocyte; cd8-positive t-lymphocytes; phenotype; glycoprotein gp 100; melanoma; phase 2 clinical trial; cell maturation; dendritic cell; granulocyte macrophage colony stimulating factor; assay; b lymphocyte; injection site reaction; lymphocyte differentiation; cytokine; double stranded dna; cellular immunity; immune response; cancer vaccines; staining; peptides; gene therapy; cell migration; effector cell; dna vaccine; phase 1 clinical trial; monophenol monooxygenase; peptide vaccine; adjuvants, immunologic; hla a antigen; vaccines, dna; vaccines, subunit; adjuvant; granulocyte macrophage colony-stimulating factors, recombinant
Journal Title: Molecular Therapy
Volume: 16
Issue: 12
ISSN: 1525-0016
Publisher: Nature Publishing Group  
Date Published: 2008-12-01
Start Page: 2022
End Page: 2029
Language: English
DOI: 10.1038/mt.2008.196
PUBMED: 18797450
PROVIDER: scopus
PMCID: PMC3909666
Notes: --- - "Cited By (since 1996): 24" - "Export Date: 17 November 2011" - "CODEN: MTOHC" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Samuel Ejadi
    4 Ejadi
  2. Jedd D Wolchok
    669 Wolchok
  3. Paul Chapman
    251 Chapman
  4. Miguel-Angel Perales
    382 Perales
  5. Katherine S Panageas
    331 Panageas
  6. Jianda Yuan
    100 Yuan
  7. Susan Krown
    87 Krown
  8. Alan N Houghton
    272 Houghton
  9. Teresa Rasalan
    25 Rasalan
  10. Sarah Powel
    5 Powel
  11. Jian Wang
    1 Wang
  12. Yan Zhang
    5 Zhang