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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of clinical oncology Jg. 23; H. 35; S. 8978
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 10.12.2005
Schlagworte:
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
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
Bibliographie: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