Lack of toxicity of therapy-induced T cell responses against the universal tumour antigen survivin.
Prognosis of disseminated melanoma remains gloomy as neither chemotherapeutic nor unspecific immune modulatory approaches were able to improve the overall survival of these patients. Hence, specific immunotherapy has received increasing attention. Disappointing clinical results, however, indicate that the choice of suitable antigens is of special importance. To this end, the inhibitor of apoptosis (IAP) protein survivin, which is over-expressed in several tumours but is largely undetectable in adult tissues, appears to be a promising target for vaccination purposes, since down-regulation or loss of expression is associated with impaired tumour progression. Consequently, five heavily pretreated stage IV melanoma patients were vaccinated with the HLA-A2 restricted survivin(96-104) epitope presented by autologous dendritic cells (DCs) in a compassionate use setting. Four of these patients mounted strong T cell responses to this epitope as measured by ELISPOT assay. Furthermore, in situ peptide/HLA-A2 multimer staining confirmed that these survivin reactive cells infiltrated both visceral and soft tissue metastases.
Otto
Kerstin
K
Department of Dermatology and Venerology, University of Würzburg, Josef-Schneider-Strasse 2, Building 13, 97080 Würzburg, Germany.
Andersen
Mads Hald
MH
Eggert
Andreas
A
Keikavoussi
Petra
P
Pedersen
Lars Østergaard
LØ
Rath
Jörg C
JC
Böck
Markus
M
Bröcker
Eva-B
EB
Straten
Per Thor
PT
Kämpgen
Eckhart
E
Becker
Jürgen C
JC
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008869:Microtubule-Associated Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D008875:Middle Aged; D009363:Neoplasm Proteins; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin