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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
Authors:Jürgen C Becker  Mads H Andersen  Valeska Hofmeister-Müller  Marion Wobser  Lidia Frey  Christiane Sandig  Steffen Walter  Harpreet Singh-Jasuja  Eckhart K?mpgen  Andreas Opitz  Marc Zapatka  Eva-B Br?cker  Per thor Straten  David Schrama  Selma Ugurel
Institution:1. Department of Dermatology, Medical University Graz, Auenbruggerplatz 8, 8010, Graz, Austria
2. Center for Cancer Immune Therapy, Department of Hematology, Herlev University Hospital, Herlev, Denmark
3. Department of Dermatology, Julius-Maximilians-University, Würzburg, Germany
4. Immatics Biotechnologies GmbH, Tübingen, Germany
5. Department of Dermatology, University Hospital Erlangen, Erlangen, Germany
6. Institute of Clinical Transfusion Medicine and Hemotherapy, Julius-Maximilians-University, Würzburg, Germany
7. Division of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg, Germany
Abstract:

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.
Keywords:
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