Survivin-specific T-cell reactivity correlates with tumor response and patient survival

• Verfasst von: Becker, Jürgen C. [VerfasserIn]
• Verfasst von: Wobser, Marion [VerfasserIn]
• Verfasst von: Zapatka, Marc [VerfasserIn]
• Titel: Survivin-specific T-cell reactivity correlates with tumor response and patient survival
• Titelzusatz: a phase-II peptide vaccination trial in metastatic melanoma
• Verf.angabe: Jürgen C. Becker, Mads H. Andersen, Valeska Hofmeister-Müller, Marion Wobser, Lidia Frey, Christiane Sandig, Steffen Walter, Harpreet Singh-Jasuja, Eckhart Kämpgen, Andreas Opitz, Marc Zapatka, Eva-B. Bröcker, Per thor Straten, David Schrama, Selma Ugurel
• E-Jahr: 2012
• Jahr: 8 May 2012
• Umfang: 13 S.
• Fussnoten: Gesehen am 27.08.2018
• Titel Quelle: Enthalten in: Cancer immunology immunotherapy
• Ort Quelle: Berlin : Springer, 1976
• Jahr Quelle: 2012
• Band/Heft Quelle: 61(2012), 11, Seite 2091-2103
• ISSN Quelle: 1432-0851
• DOI: doi:10.1007/s00262-012-1266-9
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Melanoma
• Sach-SW: Peptide vaccination
• Sach-SW: Survivin
• Sach-SW: T-cell reactivity
• Sach-SW: Therapy
• K10plus-PPN: 1580424457

Abstract

BackgroundTherapeutic 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 methodsThis 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).ResultsSixty-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.ConclusionSurvivin-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.