A phase I study of immunization using particle-mediated epidermal delivery of genes for gp100 and GM-CSF into uninvolved skin of melanoma patients

Ryan D. Cassaday, Paul M. Sondel, David M. King, Michael D. Macklin, Jacek Gan, Tom F. Warner, Cindy L. Zuleger, Alan J. Bridges, Heidi G. Schalch, Mann Kim Kyung, Jacquelyn A. Hank, David M. Mahvi, Mark R. Albertini*

*Corresponding author for this work

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Purpose: We examined in vivo particle-mediated epidermal delivery (PMED) of cDNAs for gp100 and granulocyte macrophage colony-stimulating factor (GM-CSF) into uninvolved skin of melanoma patients. The aims of this phase I study were to assess the safety and immunologic effects of PMED of these genes in melanoma patients. Experimental Design: Two treatment groups of six patients each were evaluated. Group I received PMED with cDNA for gp100, and group II received PMED with cDNA for GM-CSF followed by PMED for gp100 at the same site. One vaccine site per treatment cycle was biopsied and divided for protein extraction and sectioning to assess transgene expression, gold-bead penetration, and dendritic cell infiltration. Exploratory immunologic monitoring of HLA-A2 + patients included flow cytometric analyses of peripheral blood lymphocytes and evaluation of delayed-type hypersensitivity to gp100 peptide. Results: Local toxicity in both groups was mild and resolved within 2 weeks. No systemic toxicity could be attributed to the vaccines. Monitoring for autoimmunity showed no induction of pathologic autoantibodies. GM-CSF transgene expression in vaccinated skin sites was detected. GM-CSF and gp100 PMED yielded a greater infiltration of dendritic cells into vaccine sites than did gp100 PMED only. Exploratory immunologic monitoring suggested modest activation of an antimelanoma response. Conclusions: PMED with cDNAs for gp100 alone or in combination with GM-CSF is well tolerated by patients with melanoma. Moreover, pathologic autoimmunity was not shown. This technique yields biologically active transgene expression in normal human skin. Although modest immune responses were observed, additional investigation is needed to determine how to best utilize PMED to induce antimelanoma immune responses.

Original languageEnglish (US)
Pages (from-to)540-549
Number of pages10
JournalClinical Cancer Research
Volume13
Issue number2 I
DOIs
StatePublished - Jan 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Cassaday, R. D., Sondel, P. M., King, D. M., Macklin, M. D., Gan, J., Warner, T. F., Zuleger, C. L., Bridges, A. J., Schalch, H. G., Kyung, M. K., Hank, J. A., Mahvi, D. M., & Albertini, M. R. (2007). A phase I study of immunization using particle-mediated epidermal delivery of genes for gp100 and GM-CSF into uninvolved skin of melanoma patients. Clinical Cancer Research, 13(2 I), 540-549. https://doi.org/10.1158/1078-0432.CCR-06-2039