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Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma

Please always quote using this URN: urn:nbn:de:bvb:20-opus-126215
  • 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 oncogenicBackground 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.show moreshow less

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Author: 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
URN:urn:nbn:de:bvb:20-opus-126215
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Language:English
Parent Title (English):Cancer Immunology, Immunotherapy
Year of Completion:2012
Volume:61
Issue:11
Pagenumber:2091-2103
Source:Cancer Immunology Immunotherapy (2012) 61:2091–2103 DOI 10.1007/s00262-012-1266-9
DOI:https://doi.org/10.1007/s00262-012-1266-9
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:melanoma; peptide vaccination; survivin T-cell reactivity; therapy
Release Date:2016/07/12
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung