TY  - JOUR
A1  - Becker, Jürgen C.
A1  - Andersen, Mads H.
A1  - Hofmeister-Müller, Valeska
A1  - Wobser, Marion
A1  - Frey, Lidia
A1  - Sandig, Christiane
A1  - Walter, Steffen
A1  - Singh-Jasuja, Harpreet
A1  - Kämpgen, Eckhart
A1  - Opitz, Andreas
A1  - Zapatka, Marc
A1  - Bröcker, Eva-B.
A1  - thor Straten, Per
A1  - Schrama, David
A1  - Ugurel, Selma
T1  - Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma
JF  - Cancer Immunology, Immunotherapy
N2  - Background
Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets.

Patients and methods
This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS).

Results
Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen.

Conclusion
Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.
KW  - peptide vaccination
KW  - therapy
KW  - survivin T-cell reactivity
KW  - melanoma
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126215
VL  - 61
IS  - 11
ER  - 
TY  - JOUR
A1  - Becker, Jürgen C.
A1  - Andersen, Mads H.
A1  - Hofmeister-Müller, Valeska
A1  - Wobser, Marion
A1  - Frey, Lidia
A1  - Sandig, Christiane
A1  - Walter, Steffen
A1  - Singh-Jasuja, Harpreet
A1  - Kämpgen, Eckhart
A1  - Opitz, Andreas
A1  - Zapatka, Marc
A1  - Bröcker, Eva-B.
A1  - thor Straten, Per
A1  - Schrama, David
A1  - Ugurel, Selma
T1  - Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma
JF  - Cancer Immunology, Immunotherapy
N2  - Background
Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets.

Patients and methods
This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS).

Results
Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen.

Conclusion
Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.
KW  - peptide vaccination
KW  - melanoma
KW  - survivin
KW  - T-cell reactivity
KW  - therapy
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124830
VL  - 61
IS  - 11
ER  -