Hybrid cell vaccination in metastatic melanoma: clinical and immunologic results of a phase I/II study.
Hybrid cell vaccination with cell fusion products (CFPs) of autologous tumor cells and mature allogenic MHC II bearing dendritic cells has been described to induce cytotoxic T lymphocyte (CTL)-mediated immune responses. The aim of this study was to assess safety, antitumor activity, and immune responses of a CFP-vaccine in patients with disseminated malignant melanoma. In a phase I/II study, we treated 11 patients by monthly intracutaneous or subcutaneous application of a CFP vaccine generated by electrofusion of autologous melanoma cells with mature allogenic dendritic cells. In addition, patients received subcutaneous low-dose interleukin-2 injections for 6 days after each vaccination. No serious adverse effects were observed. Ten patients showed progressive disease and one patient had a short-lasting stable disease. None of the patients developed a positive delayed-type hypersensitivity reaction against irradiated autologous melanoma cells. In 2 patients, who were monitored in more detail, we found no evidence of induction of a specific antimelanoma T-cell response by analyzing the proliferation, cytokine secretion, and cytotoxicity of their T cells toward autologous melanoma cells. No unequivocal beneficial effects of the used CFP vaccine could be demonstrated.
Haenssle
Holger A
HA
Department of Dermatology, Georg-August-University Goettingen, Germany. h.haenssle@med.uni-goettingen.de
Krause
Stefan W
SW
Emmert
Steffen
S
Zutt
Markus
M
Kretschmer
Lutz
L
Schmidberger
Heinz
H
Andreesen
Reinhard
R
Soruri
Afsaneh
A
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines; D002455:Cell Division; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006822:Hybrid Cells; D007167:Immunotherapy / Q000379:methods*; D020287:In Situ Nick-End Labeling; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
D019496:Cancer Vaccines