Multiplex bead-based measurement of humoral immune responses against tumor-associated antigens in stage II melanoma patients of the EORTC18961 trial

Purpose: Determine the prognostic and predictive significance of tumor associated antigen (TAA)-specific serum antibodies in melanoma patients of a large adjuvant vaccination phase III trial. Patients and methods: Serum IgG antibodies were measured against a panel of 43 antigens by a bead-based mult...

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Hauptverfasser: Michels, Judith (VerfasserIn) , Becker, Natalia (VerfasserIn) , Suciu, Stefan (VerfasserIn) , Kaiser, Iris (VerfasserIn) , Benner, Axel (VerfasserIn) , Kosaloglu-Yalcin, Zeynep (VerfasserIn) , Agoussi, Sandrine (VerfasserIn) , Halama, Niels (VerfasserIn) , Pawlita, Michael (VerfasserIn) , Waterboer, Tim (VerfasserIn) , Eichmüller, Stefan B. (VerfasserIn) , Jäger, Dirk (VerfasserIn) , Eggermont, Alexander M. M. (VerfasserIn) , Zörnig, Inka (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 12 February 2018
In: OncoImmunology
Year: 2018, Jahrgang: 7, Heft: 6
ISSN:2162-402X
DOI:10.1080/2162402X.2018.1428157
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1080/2162402X.2018.1428157
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Verfasserangaben:Judith Michels, Natalia Becker, Stefan Suciu, Iris Kaiser, Axel Benner, Zeynep Kosaloglu-Yalcin, Sandrine Agoussi, Niels Halama, Michael Pawlita, Tim Waterboer, Stefan B. Eichmüller, Dirk Jäger, Alexander M.M. Eggermont & Inka Zörnig

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520 |a Purpose: Determine the prognostic and predictive significance of tumor associated antigen (TAA)-specific serum antibodies in melanoma patients of a large adjuvant vaccination phase III trial. Patients and methods: Serum IgG antibodies were measured against a panel of 43 antigens by a bead-based multiplex assay in 970 stage II melanoma patients of the EORTC18961 trial, evaluating adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation. Primary end point was relapse-free survival (RFS). Patients' sera at baseline, after 12 and 48 weeks of study treatment and at the last available time point (at recurrence/remission) were evaluated. Results: Prognostic clinical variables are gender, surgical confirmation of lymph node-negative status, Breslow thickness and ulceration of the primary. Prognostic spontaneous antibody responses were associated with a significant dismal (GM2, Rhod_E2, SSX2) or good prognosis (CyclinB1, SCYE1v1) for RFS, distant metastasis-free (DMFS) or overall survival (OS). Predictive spontaneous antibody responses based on significant interaction with treatment were RhodN p = 0.02, Rab38 p = 0.04 for RFS, RhodE2 p = 0.006, Recoverin p = 0.04 for DMFS and RhodE2 p = 0.003; Recoverin p = 0.04, NA17.A p = 0.04, for OS respectively. The subgroups of patients according to antibody responses for RFS were determined for RhodN sero-negative (n = 849, HR = 1.07, p = 0.6); RhodN sero-positive (n = 121,HR = 0.42, p = 0.01) and Rab38 sero-negative (n = 682, HR = 1.12, p = 0.42), Rab38 sero-positive (n = 288, HR = 0.65, p = 0.04) patients respectively. Conclusion: We identified prognostic serum antibody responses against TAA in stage II melanoma patients. A set of antibody responses correlated with a beneficial outcome for GM2 vaccination. 
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