Clinical and immunologic results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells.
OBJECTIVE
To determine clinical and immunologic responses to a multipeptide melanoma vaccine regimen, a randomized phase II trial was performed.


METHODS
Twenty-six patients with advanced melanoma were randomly assigned to vaccination with a mixture of four gp100 and tyrosinase peptides restricted by HLA-A1, HLA-A2, and HLA-A3, plus a tetanus helper peptide, either in an emulsion with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Montanide ISA-51 adjuvant (Seppic Inc, Fairfield, NJ), or pulsed on monocyte-derived dendritic cells (DCs). Systemic low-dose interleukin-2 (Chiron, Emeryville, CA) was given to both groups. T-lymphocyte responses were assessed, by interferon gamma ELIspot assay (Chiron, Emeryville, CA), in peripheral-blood lymphocytes (PBLs) and in a lymph node draining a vaccine site (sentinel immunized node [SIN]).


RESULTS
In patients vaccinated with GM-CSF in adjuvant, T-cell responses to melanoma peptides were observed in 42% of PBLs and 80% of SINs, but in patients vaccinated with DCs, they were observed in only 11% and 13%, respectively. The overall immune response was greater in the GM-CSF arm (P <.02). Vitiligo developed in two of 13 patients in the GM-CSF arm but in no patients in the DC arm. Helper T-cell responses to the tetanus peptide were detected in PBLs after vaccination and correlated with T-cell reactivity to the melanoma peptides. Objective clinical responses were observed in two patients in the GM-CSF arm and one patient in the DC arm. Stable disease was observed in two patients in the GM-CSF arm and one patient in the DC arm.


CONCLUSIONS
The high frequency of cytotoxic T-lymphocyte responses and the occurrence of clinical tumor regressions support continued investigation of multipeptide vaccines administered with GM-CSF in adjuvant.
Department of Surgery/Division of Surgical Oncology, University of Virginia, Charlottesville, 22908, USA. cls8h@virginia.edu
Craig L
CL
Slingluff
Gina R
GR
Petroni
Galina V
GV
Yamshchikov
Donna L
DL
Barnd
Shannon
S
Eastham
Holly
H
Galavotti
James W
JW
Patterson
Donna H
DH
Deacon
Sarah
S
Hibbitts
David
D
Teates
Patrice Y
PY
Neese
William W
WW
Grosh
Kimberly A
KA
Chianese-Bullock
Elizabeth M H
EM
Woodson
Catherine J
CJ
Wiernasz
Priscilla
P
Merrill
Jennifer
J
Gibson
Maureen
M
Ross
Victor H
VH
Engelhard
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003713:Dendritic Cells; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000556:secondary; D008562:Membrane Glycoproteins / Q000008:administration & dosage; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000008:administration & dosage; D009829:Oleic Acids / Q000008:administration & dosage; D010446:Peptide Fragments / Q000008:administration & dosage; D011859:Radiography; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D013899:Thoracic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000556:secondary; D016896:Treatment Outcome; D058951:gp100 Melanoma Antigen
D019496:Cancer Vaccines; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009829:Oleic Acids; C548637:PMEL protein, human; D010446:Peptide Fragments; D058951:gp100 Melanoma Antigen; C477385:montanide ISA 51; D008353:Mannitol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014442:Monophenol Monooxygenase