Complete remission of liver metastasis of pancreatic cancer under vaccination with a HLA-A2 restricted peptide derived from the universal tumor antigen survivin.
OBJECTIVE
As prognosis of advanced pancreatic cancer remains gloomy, novel therapeutic modalities have to be developed. Immunotherapy, which targets tumor-associated antigens of tumor cells or tumor stroma, is currently under investigation. As survivin is expressed by neoplastic and tumor endothelial cells, but rarely by normal cells, this antigen appears as an intriguing target molecule.


METHODS
A 72-year old patient, suffering from pancreatic cancer refractory to gemcitabine therapy, received the survivin-based peptide vaccinations consisting of 100 mug of a modified HLA-A2 restricted survivin(96-104) epitope in Montanide(R). Each visit the patient was assessed for adverse events, quality of life and immunological response. Immuno-monitoring was performed by IFN-gamma-ELISPOT analysis of peripheral blood lymphocytes. Clinical outcome was evaluated by repetitive computed tomography.


RESULTS
Under vaccination with survivin peptides the patient initially underwent partial remission of liver metastasis which proceeded after 6 months into a complete remission with a duration of 8 months. Immunological monitoring revealed strong vaccine-induced immune-reactivity against survivin. Unfortunately, after the patient was weaned from vaccination in state of no evidence of disease, he developed recurrent disease.


CONCLUSIONS
T-cell responses against survivin-expressing cells of the tumor itself and tumor endothelium should impact tumor growth and metastasis. The presented patient with pancreatic cancer is the first example of a successful application of a survivin-based vaccination in the clinical setting. An ongoing phase I/II trial with HLA-A1, -A2 and -B35 restricted survivin peptides for patients with advanced cancer will provide further information towards this notion.
Wobser
Marion
M
Department of Dermatology and Venerology, University of Wuerzburg, Josef-Schneider-Strasse 2, Building 13, 97080 Wuerzburg, Germany.
Keikavoussi
Petra
P
Kunzmann
Volker
V
Weininger
Markus
M
Andersen
Mads H
MH
Becker
Juergen C
JC
D000230:Adenocarcinoma / Q000556:secondary*; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D051034:Inhibitor of Apoptosis Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000627:therapeutic use*; D009363:Neoplasm Proteins / Q000276:immunology / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology; D014057:Tomography, X-Ray Computed
C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D000077022:Survivin; D007371:Interferon-gamma