TY - JOUR
T1 - Multiplex bead-based measurement of humoral immune responses against tumor-associated antigens in stage II melanoma patients of the EORTC18961 trial
AU - Michels, Judith
AU - Becker, Natalia
AU - Suciu, Stefan
AU - Kaiser, Iris
AU - Benner, Axel
AU - Kosaloglu-Yalcin, Zeynep
AU - Agoussi, Sandrine
AU - Halama, Niels
AU - Pawlita, Michael
AU - Waterboer, Tim
AU - Eichmüller, Stefan B.
AU - Jäger, Dirk
AU - Eggermont, Alexander M.M.
AU - Zörnig, Inka
N1 - Publisher Copyright:
© 2018 The Author(s). Published with license by Taylor & Francis Group, LLC © 2018, © 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 and Inka Zörnig.
PY - 2018/6/3
Y1 - 2018/6/3
N2 - 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.
AB - 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.
KW - autoantibody
KW - ganglioside
KW - melanoma
KW - multiplex serology
KW - rhodopsin
UR - http://www.scopus.com/inward/record.url?scp=85041916616&partnerID=8YFLogxK
U2 - 10.1080/2162402X.2018.1428157
DO - 10.1080/2162402X.2018.1428157
M3 - Article
C2 - 29872552
AN - SCOPUS:85041916616
SN - 2162-4011
VL - 7
JO - OncoImmunology
JF - OncoImmunology
IS - 6
M1 - e1428157
ER -