Helper T-cell responses and clinical activity of a melanoma vaccine with multiple peptides from MAGE and melanocytic differentiation antigens.
OBJECTIVE
A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel melanoma vaccine comprising six melanoma-associated peptides defined as antigenic targets for melanoma-reactive helper T cells. Source proteins for these peptides include MAGE proteins, MART-1/MelanA, gp100, and tyrosinase.


METHODS
Thirty-nine patients with stage IIIB to IV melanoma were vaccinated with this six-peptide mixture weekly at three dose levels, with a preceding phase I dose escalation and subsequent random assignment among the dose levels. Helper T-lymphocyte responses were assessed by in vitro proliferation assay and delayed-type hypersensitivity skin testing. Patients with measurable disease were evaluated for objective clinical response by Response Evaluation Criteria in Solid Tumors.


RESULTS
Vaccination with the helper peptide vaccine was well tolerated. Proliferation assays revealed induction of T-cell responses to the melanoma helper peptides in 81% of patients. Among 17 patients with measurable disease, objective clinical responses were observed in two patients (12%), with response durations of 1 and 3.9+ years. Durable stable disease was observed in two additional patients for periods of 1.8 and 4.6+ years.


CONCLUSIONS
Results of this study support the safety and immunogenicity of a vaccine comprised of six melanoma helper peptides. There is also early evidence of clinical activity.
Slingluff
Craig L
CL
Department of Surgery/Division of Surgical Oncology, University of Virginia Health System, Charlottesville, VA 22908, USA. cls8h@virginia.edu
Petroni
Gina R
GR
Olson
Walter
W
Czarkowski
Andrea
A
Grosh
William W
WW
Smolkin
Mark
M
Chianese-Bullock
Kimberly A
KA
Neese
Patrice Y
PY
Deacon
Donna H
DH
Nail
Carmel
C
Merrill
Priscilla
P
Fink
Robyn
R
Patterson
James W
JW
Rehm
Patrice K
PK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000943:Antigens, Differentiation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000633:toxicity*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D058965:MART-1 Antigen; D008297:Male; D008544:Melanocytes / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D012882:Skin Tests; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014820:Vitiligo / Q000139:chemically induced; D058951:gp100 Melanoma Antigen
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase