Antibodies as biomarker candidates for response and survival to checkpoint inhibitors in melanoma patients
| Autor: | Fässler, Mirjam, Diem, Stefan, Mangana, Joanna, Hasan Ali, Omar, Berner, Fiamma, Bomze, David, Ring, Sandra, Niederer, Rebekka, Del Carmen Gil Cruz, Cristina, Pérez Shibayama, Christian Ivan, Krolik, Michal, Siano, Marco, Joerger, Markus, Recher, Mike, Risch, Lorenz, Güsewell, Sabine, Risch, Martin, Speiser, Daniel E, Ludewig, Burkhard, Levesque, Mitchell P, Dummer, Reinhard, Flatz, Lukas |
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| Přispěvatelé: | University of Zurich, Flatz, Lukas |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Antibodies Neoplasm 610 Medicine & health Metastatic melanoma Antibodies Monoclonal Humanized lcsh:RC254-282 Antibodies TRP2 TRP1 Antineoplastic Agents Immunological Humans NY-ESO-1 1306 Cancer Research Immune response Melanoma Aged Aged 80 and over 2403 Immunology 10177 Dermatology Clinic Biomarker Middle Aged lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ipilimumab 3004 Pharmacology Nivolumab gp100 1313 Molecular Medicine Immunoglobulin G 2723 Immunology and Allergy Melanocyte differentiation antigens MART1 2730 Oncology Antibodies Monoclonal Humanized/therapeutic use Antibodies Neoplasm/blood Antineoplastic Agents Immunological/therapeutic use Biomarkers Female Immunoglobulin G/blood Ipilimumab/therapeutic use Melanoma/blood Melanoma/drug therapy Melanoma/immunology Nivolumab/therapeutic use Cancer/testis antigens Checkpoint inhibitors Research Article |
| Zdroj: | Fässler, Mirjam; Diem, Stefan; Mangana, Joanna; Hasan Ali, Omar; Berner, Fiamma; Bomze, David; Ring, Sandra; Niederer, Rebekka; Del Carmen Gil Cruz, Cristina; Pérez Shibayama, Christian Ivan; Krolik, Michal; Siano, Marco; Joerger, Markus; Recher, Mike; Risch, Lorenz; Güsewell, Sabine; Risch, Martin; Speiser, Daniel E; Ludewig, Burkhard; Levesque, Mitchell P; ... (2019). Antibodies as biomarker candidates for response and survival to checkpoint inhibitors in melanoma patients. Journal for immunotherapy of cancer, 7(1), p. 50. BioMed Central 10.1186/s40425-019-0523-2 Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-12 (2019) Journal for Immunotherapy of Cancer Journal for immunotherapy of cancer, vol. 7, no. 1, pp. 50 |
| DOI: | 10.1186/s40425-019-0523-2 |
| Popis: | Background Long-term survival of stage IV melanoma patients has improved significantly with the development of immune checkpoint inhibitors (CIs). Reliable biomarkers to predict response and clinical outcome are needed. Methods We investigated the role of melanoma-associated antibodies as predictive markers for CI therapy in two independent cohorts. In cohort 1, a prospective study, we measured specific antibodies before treatment, after one week and after six to nine weeks of treatment. Cohort 2 consisted of serum samples prior to CI therapy initiation. ELISA assays were performed to quantify specific IgG directed against melanocyte differentiation antigens tyrosinase-related proteins 1 and 2 (TRP1/TYRP1 and TRP2/TYRP2), glycoprotein 100 (gp100), MelanA/MART1, and the cancer-testis antigen NY-ESO-1. Response was defined as either complete or partial remission on CT scan according to RECIST 1.1. Results In cohort 1, baseline levels of these antibodies were higher in the responder group, although statistical significance was only reached for NY-ESO-1 (p = 0.007). In cohort 2, significantly higher antibody baseline levels for MelanA/MART1 (p = 0.003) and gp100 (p = 0.029) were found. After pooling the results from both cohorts, higher levels of MelanA/MART1 (p = 0.013), TRP1/TYRP1 (p = 0.048), TRP2/TYRP2 (p = 0.047) and NY-ESO-1 (p = 0.005) specific antibodies at baseline were independently associated with response. Conclusions Melanoma-associated antibodies may be candidate biomarkers for response and survival in metastatic melanoma patients being treated with CIs. These markers may be used to complement patient assessment, in combination with PD-L1 status, tumor-infiltrating lymphocytes and tumor mutational burden, with the aim to predict outcome of CI treatment in patients with metastatic melanoma. Trial registration Ethikkommission Ostschweiz, EKOS 16/079 https://ongoingprojects.swissethics.ch/runningProjects_list.php?q=%28BASECID~contains~2016-00998%29&orderby=dBASECID. Electronic supplementary material The online version of this article (10.1186/s40425-019-0523-2) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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