Long-term freedom from recurrence in 2 stage IV melanoma patients following vaccination with tyrosinase peptides.
We report here on 2 patients who received adjuvant vaccination with an HLA-A2- or HLA-A24-restricted tyrosinase peptide, respectively, and GM-CSF for frequently relapsing stage IV melanoma. Following resection of metastases and irradiation of brain metastases in 1 patient, both patients were without evidence of disease when receiving the first vaccination. While the patients had had 9 and 12, respectively, mostly s.c., relapses during the 3 years before vaccination, they experienced freedom from relapse for more than 2 years after vaccination. We found a T-cell response to the vaccine peptide in both patients in the peripheral blood by ex vivo IFN-gamma ELISPOT assay. The T-cell population could be further characterized by 4-color flow cytometry in 1 patient, showing that the majority of the peptide-specific CD3(+)CD8(+)IFN-gamma(+) T cells were granzyme B-positive and CCR-7-negative, characterizing them as effector T cells with the ability to mediate cytotoxicity and migrate to inflamed tissues. In this patient also, augmentation of the T-cell response to autologous tumor cells by vaccination could be detected. A single-site postvaccination relapse occurred in both patients, showing downregulation of tyrosinase expression in 1 patient, while normal expression levels for tyrosinase, MHC class I antigens and components of the antigen-processing machinery were found in the other patient. These results suggest that peptide vaccination resulted in a prolonged relapse-free interval in these high-risk patients.
Scheibenbogen
Carmen
C
Medizinische Klinik III, Hämatologie, Onkologie und Transfusionsmedizin, Universitätsklinikum Benjamin-Franklin, Freie Universität Berlin, Berlin, Germany.
Nagorsen
Dirk
D
Seliger
Barbara
B
Schmittel
Alexander
A
Letsch
Anne
A
Bauer
Sandra
S
Max
Nicole
N
Bock
Michaela
M
Atkins
Derek
D
Thiel
Eckhard
E
Keilholz
Ulrich
U
D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary; D017252:CD3 Complex / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D019496:Cancer Vaccines; D018572:Disease-Free Survival; D000939:Epitopes; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D008545:Melanoma / Q000175:diagnosis* / Q000473:pathology / Q000517:prevention & control*; D014442:Monophenol Monooxygenase / Q000627:therapeutic use*; D009362:Neoplasm Metastasis; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
D017252:CD3 Complex; D016827:CD8 Antigens; D019496:Cancer Vaccines; D000939:Epitopes; D010455:Peptides; D012333:RNA, Messenger; D007371:Interferon-gamma; D014442:Monophenol Monooxygenase