Current strategies for the immunotherapy of melanoma include augmentation of the immune response to tumor antigens represented by melanosomal proteins such as tyrosinase, gp100, and MART-1. The possibility that intentional targeting of tumor antigens representing normal proteins can result in autoimmune toxicity has been postulated but never demonstrated previously in humans. In this study, we describe a patient with metastatic melanoma who developed inflammatory lesions circumscribing pigmented areas of skin after an infusion of MART-1–specific CD8+ T cell clones. Analysis of the infiltrating lymphocytes in skin and tumor biopsies using T cell–specific peptide–major histocompatibility complex tetramers demonstrated a localized predominance of MART-1–specific CD8+ T cells (>28% of all CD8 T cells) that was identical to the infused clones (as confirmed by sequencing of the complementarity-determining region 3). In contrast to skin biopsies obtained from the patient before T cell infusion, postinfusion biopsies demonstrated loss of MART-1 expression, evidence of melanocyte damage, and the complete absence of melanocytes in affected regions of the skin. This study provides, for the first time, direct evidence in humans that antigen-specific immunotherapy can target not only antigen-positive tumor cells in vivo but also normal tissues expressing the shared tumor antigen.
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4 December 2000
Brief Definitive Report|
December 04 2000
Melanocyte Destruction after Antigen-Specific Immunotherapy of Melanoma: Direct Evidence of T Cell–Mediated Vitiligo
Cassian Yee,
Cassian Yee
aClinical Research Division, Fred Hutchinson Cancer Research Center, the
bDepartment of Medicine, University of Washington, Seattle, Washington 98109
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John A. Thompson,
John A. Thompson
bDepartment of Medicine, University of Washington, Seattle, Washington 98109
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Patrick Roche,
Patrick Roche
dDepartment of Pathology, Mayo Clinic, Rochester, Minnesota 55905
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David R. Byrd,
David R. Byrd
cDepartment of Surgery, University of Washington, Seattle, Washington 98109
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Peter P. Lee,
Peter P. Lee
eDepartment of Microbiology and Immunology, Stanford University, Stanford, California 94305
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Michael Piepkorn,
Michael Piepkorn
bDepartment of Medicine, University of Washington, Seattle, Washington 98109
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Karla Kenyon,
Karla Kenyon
aClinical Research Division, Fred Hutchinson Cancer Research Center, the
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Mark M. Davis,
Mark M. Davis
eDepartment of Microbiology and Immunology, Stanford University, Stanford, California 94305
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Stanley R. Riddell,
Stanley R. Riddell
aClinical Research Division, Fred Hutchinson Cancer Research Center, the
bDepartment of Medicine, University of Washington, Seattle, Washington 98109
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Philip D. Greenberg
Philip D. Greenberg
aClinical Research Division, Fred Hutchinson Cancer Research Center, the
bDepartment of Medicine, University of Washington, Seattle, Washington 98109
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Cassian Yee
aClinical Research Division, Fred Hutchinson Cancer Research Center, the
bDepartment of Medicine, University of Washington, Seattle, Washington 98109
John A. Thompson
bDepartment of Medicine, University of Washington, Seattle, Washington 98109
Patrick Roche
dDepartment of Pathology, Mayo Clinic, Rochester, Minnesota 55905
David R. Byrd
cDepartment of Surgery, University of Washington, Seattle, Washington 98109
Peter P. Lee
eDepartment of Microbiology and Immunology, Stanford University, Stanford, California 94305
Michael Piepkorn
bDepartment of Medicine, University of Washington, Seattle, Washington 98109
Karla Kenyon
aClinical Research Division, Fred Hutchinson Cancer Research Center, the
Mark M. Davis
eDepartment of Microbiology and Immunology, Stanford University, Stanford, California 94305
Stanley R. Riddell
aClinical Research Division, Fred Hutchinson Cancer Research Center, the
bDepartment of Medicine, University of Washington, Seattle, Washington 98109
Philip D. Greenberg
aClinical Research Division, Fred Hutchinson Cancer Research Center, the
bDepartment of Medicine, University of Washington, Seattle, Washington 98109
Received:
July 24 2000
Revision Requested:
October 03 2000
Accepted:
October 13 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 192 (11): 1637–1644.
Article history
Received:
July 24 2000
Revision Requested:
October 03 2000
Accepted:
October 13 2000
Citation
Cassian Yee, John A. Thompson, Patrick Roche, David R. Byrd, Peter P. Lee, Michael Piepkorn, Karla Kenyon, Mark M. Davis, Stanley R. Riddell, Philip D. Greenberg; Melanocyte Destruction after Antigen-Specific Immunotherapy of Melanoma: Direct Evidence of T Cell–Mediated Vitiligo. J Exp Med 4 December 2000; 192 (11): 1637–1644. doi: https://doi.org/10.1084/jem.192.11.1637
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