Immunologic response to xenogeneic gp100 DNA in melanoma patients: Comparison of particle-mediated epidermal delivery with intramuscular injection Journal Article


Authors: Ginsberg, B. A.; Gallardo, H. F.; Rasalan, T. S.; Adamow, M.; Mu, Z.; Tandon, S.; Bewkes, B. B.; Roman, R. A.; Chapman, P. B.; Schwartz, G. K.; Carvajal, R. D.; Panageas, K. S.; Terzulli, S. L.; Houghton, A. N.; Yuan, J. D.; Wolchok, J. D.
Article Title: Immunologic response to xenogeneic gp100 DNA in melanoma patients: Comparison of particle-mediated epidermal delivery with intramuscular injection
Abstract: Purpose: Prior studies show that i.m. injection of xenogeneic orthologues of melanosomal antigens (tyrosinase, gp100) induces CD8+ T-cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a pilot clinical trial comparing i.m. injection with particle-mediated epidermal delivery (PMED). Experimental Design: Human leukocyte antigen (HLA)-A*0201+ disease-free melanoma patients were randomized to the PMED or i.m. arm, receiving eight vaccinations over 4 months. Patients received 4 μg or 2,000 μg per injection, respectively, of mouse gp100 DNA. Peripheral blood mononuclear cells were collected, cultured with gp100 peptides, and analyzed by tetramer and intracellular cytokine staining for responses to HLA-A*0201-restricted gp100 epitopes [gp100 209-217 (ITDQVPFSV) and gp100280-288 (YLEPGPVTA)]. Results: Twenty-seven patients with stage IIB-IV melanoma were analyzable for immune response. The only common toxicity was grade 1 injection site reaction in nine patients with no intergroup difference, and one dose-limiting toxicity of acute hypersensitivity occurred in a PMED patient with undiagnosed gold allergy. Four of 27 patients produced gp100 tetramer+CD8+ T cells, all carrying the CCR7loCD45RAlo effector-memory phenotype. Five of 27 patients generated IFN-γ+CD8+ T cells, one who was also tetramer-positive. Overall, vaccination induced a response in 30% of patients, which was not significantly associated with study arm or clinical outcome. However, the PMED group showed a trend toward increased IFN-γ+CD8+ T-cell generation (P = 0.07). Conclusion: A comparable efficacy and safety profile was shownbetween the i.m. and PMED arms, despite a significantly decreased dose of DNA used for PMED injection. ©2010 AACR.
Keywords: adult; clinical article; controlled study; aged; middle aged; clinical trial; fatigue; alpha interferon; cancer staging; neoplasm staging; cd8+ t lymphocyte; cd8-positive t-lymphocytes; phenotype; animals; mice; glycoprotein gp 100; interleukin 2; melanoma; controlled clinical trial; drug eruption; allergy; nausea; randomized controlled trial; myalgia; cell population; abdominal pain; arthralgia; drug hypersensitivity; injection site reaction; pruritus; kaplan-meiers estimate; cytokine; dna; cell culture; cancer vaccines; pilot projects; membrane glycoproteins; gout; hla a antigen; chemokine receptor ccr7; vaccines, dna; hla-a antigens; peripheral blood mononuclear cell; cd45ra antigen; plasmid dna; gold; epiphora; administration, intranasal; antigens, heterophile; biolistics
Journal Title: Clinical Cancer Research
Volume: 16
Issue: 15
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2010-08-01
Start Page: 4057
End Page: 4065
Language: English
DOI: 10.1158/1078-0432.ccr-10-1093
PUBMED: 20647477
PROVIDER: scopus
PMCID: PMC4241567
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Gary Schwartz
    358 Schwartz
  2. Jedd D Wolchok
    656 Wolchok
  3. Richard D Carvajal
    133 Carvajal
  4. Paul Chapman
    246 Chapman
  5. Ruth-Ann Roman
    27 Roman
  6. Katherine S Panageas
    327 Panageas
  7. Jianda Yuan
    100 Yuan
  8. Alan N Houghton
    267 Houghton
  9. Barrett Bowling Bewkes
    2 Bewkes
  10. Teresa Rasalan
    25 Rasalan
  11. Matthew J Adamow
    10 Adamow
  12. Zhenyu Mu
    10 Mu
  13. Sapna Tandon
    5 Tandon