Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma
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....
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
8 May 2012
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| In: |
Cancer immunology immunotherapy
Year: 2012, Jahrgang: 61, Heft: 11, Pages: 2091-2103 |
| ISSN: | 1432-0851 |
| DOI: | 10.1007/s00262-012-1266-9 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1007/s00262-012-1266-9 Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s00262-012-1266-9 
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| Verfasserangaben: | 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 |
| Zusammenfassung: | 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. |
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| Beschreibung: | Gesehen am 27.08.2018 |
| Beschreibung: | Online Resource |
| ISSN: | 1432-0851 |
| DOI: | 10.1007/s00262-012-1266-9 |