Immunogenicity, including vitiligo, and feasibility of vaccination with autologous GM-CSF-transduced tumor cells in metastatic melanoma patients

To determine the feasibility, toxicity, and immunologic effects of vaccination with autologous tumor cells retrovirally transduced with the GM-CSF gene, we performed a phase I/II vaccination study in stage IV metastatic melanoma patients. Sixty-four patients were randomly assigned to receive three v...

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Podrobná bibliografia
Vydané v:	Journal of clinical oncology Ročník 23; číslo 35; s. 8978
Hlavní autori:	Luiten, Rosalie M, Kueter, Esther W M, Mooi, Wolter, Gallee, Maarten P W, Rankin, Elaine M, Gerritsen, Winald R, Clift, Shirley M, Nooijen, Willem J, Weder, Pauline, van de Kasteele, Willeke F, Sein, Johan, van den Berk, Paul C M, Nieweg, Omgo E, Berns, Anton M, Spits, Hergen, de Gast, Gijsbert C
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 10.12.2005
Predmet:	Adjuvants, Immunologic Adult Aged Antigens, Neoplasm - immunology Autoimmune Diseases - etiology Cancer Vaccines - adverse effects Cancer Vaccines - immunology Cancer Vaccines - therapeutic use Cytotoxicity, Immunologic Drug Administration Schedule Feasibility Studies Female Granulocyte-Macrophage Colony-Stimulating Factor - adverse effects Granulocyte-Macrophage Colony-Stimulating Factor - immunology Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use Humans Male Melanoma - drug therapy Melanoma - immunology Middle Aged Neoplasm Proteins - immunology Peptide Fragments - immunology T-Lymphocytes - immunology Vitiligo - etiology
ISSN:	0732-183X
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Popis
Shrnutí:	To determine the feasibility, toxicity, and immunologic effects of vaccination with autologous tumor cells retrovirally transduced with the GM-CSF gene, we performed a phase I/II vaccination study in stage IV metastatic melanoma patients. Sixty-four patients were randomly assigned to receive three vaccinations of high-dose or low-dose tumor cells at 3-week intervals. Tumor cell vaccine preparation succeeded for 56 patients (88%), but because of progressive disease, the well-tolerated vaccination was completed in only 28 patients. We analyzed the priming of T cells against melanoma antigens, MART-1, tyrosinase, gp100, MAGE-A1, and MAGE-A3 using human leukocyte antigen/peptide tetramers and functional assays. The high-dose vaccination induced the infiltration of T cells into the tumor tissue. Three of 14 patients receiving the high-dose vaccine showed an increase in MART-1- or gp100-specific T cells in the peripheral blood during vaccination. Six patients experienced disease-free survival for more than 5 years, and two of these patients developed vitiligo at multiple sites after vaccination. MART-1- and gp100-specific T cells were found infiltrating in vitiligo skin. Upon vaccination, the T cells acquired an effector phenotype and produced interferon-gamma on specific antigenic stimulation. We conclude that vaccination with GM-CSF-transduced autologous tumor cells has limited toxicity and can enhance T-cell activation against melanocyte differentiation antigens, which can lead to vitiligo. Whether the induction of autoimmune vitiligo may prolong disease-free survival of metastatic melanoma patients who are surgically rendered as having no evidence of disease before vaccination is worthy of further investigation.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	0732-183X
DOI:	10.1200/JCO.2005.01.6816