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 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 journalArticle

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
Externally publishedYes

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gp100 Melanoma Antigen
Melanocytes
Melanoma
Plasmids
DNA
Immunization
Poxviridae
Neoplasm Antigens
T-Lymphocytes
Antigens
Skin
Peptides

ASJC Scopus subject areas

  • Genetics

Cite this

Inability to immunize patients with metastatic melanoma using plasmid DNA encoding the gp100 melanoma-melanocyte antigen. / Rosenberg, Steven A.; Yang, James C.; Sherry, Richard M.; Hwu, Patrick; Topalian, Suzanne; Schwartzentruber, Douglas J.; Restifo, Nicholas P.; Haworth, Leah R.; Seipp, Claudia A.; Freezer, Linda J.; Morton, Kathleen E.; Mavroukakis, Sharon A.; White, Donald E.

In: Human Gene Therapy, Vol. 14, No. 8, 20.05.2003, p. 709-714.

Research output: Contribution to journalArticle

Rosenberg, SA, Yang, JC, Sherry, RM, Hwu, P, Topalian, S, Schwartzentruber, DJ, Restifo, NP, Haworth, LR, Seipp, CA, Freezer, LJ, Morton, KE, Mavroukakis, SA & White, DE 2003, 'Inability to immunize patients with metastatic melanoma using plasmid DNA encoding the gp100 melanoma-melanocyte antigen', Human Gene Therapy, vol. 14, no. 8, pp. 709-714. https://doi.org/10.1089/104303403765255110
Rosenberg, Steven A. ; Yang, James C. ; Sherry, Richard M. ; Hwu, Patrick ; Topalian, Suzanne ; Schwartzentruber, Douglas J. ; Restifo, Nicholas P. ; Haworth, Leah R. ; Seipp, Claudia A. ; Freezer, Linda J. ; Morton, Kathleen E. ; Mavroukakis, Sharon A. ; White, Donald E. / Inability to immunize patients with metastatic melanoma using plasmid DNA encoding the gp100 melanoma-melanocyte antigen. In: Human Gene Therapy. 2003 ; Vol. 14, No. 8. pp. 709-714.
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