Inability to immunize patients with metastatic melanoma using plasmid DNA encoding the gp100 melanoma-melanocyte antigen

Steven A. Rosenberg, James C. Yang, Richard M. Sherry, Patrick Hwu, Suzanne L. Topalian, Douglas J. Schwartzentruber, Nicholas P. Restifo, Leah R. Haworth, Claudia A. Seipp, Linda J. Freezer, Kathleen E. Morton, Sharon A. Mavroukakis, Donald E. White

Research output: Contribution to journalArticlepeer-review

Abstract

Immunization with plasmid DNA represents a theoretically attractive method for increasing T cell responses against cancer antigens. We administered plasmid DNA encoding the gp100 melanoma-melanocyte differentiation antigen to 22 patients with metastatic melanoma and evaluated immunologic and clinical responses. Patients were randomized to receive plasmid DNA either intradermally (n = 10) or intramuscularly (n = 12). One patient (4.5%) exhibited a partial response of several subcentimeter cutaneous nodules. All other patients had progressive disease. Of 13 patients with cells available before and after immunization, no patient exhibited evidence of the development of anti-gp100 cell responses using in vitro boost assays. The same assays were capable of demonstrating immunologic precursors after immunization with fowl poxvirus encoding gp100 or with gp100 peptides. We were thus unable to demonstrate significant clinical or immunologic responses to plasmid DNA encoding the "self" nonmutated gp100 tumor antigen.

Original languageEnglish (US)
Pages (from-to)709-714
Number of pages6
JournalHuman gene therapy
Volume14
Issue number8
DOIs
StatePublished - May 20 2003

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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