Expression of the tumor antigens NY-ESO-1, tyrosinase, MAGE-A3, and TPTE in pediatric and adult melanoma: a retrospective case control study.

Autor: Forchhammer S; Department of Dermatology, Eberhard Karls University of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany. stephan.forchhammer@med.uni-tuebingen.de., Pop OT; Institute for Immunobiology, Kantonsspital St Gallen, St Gallen, Switzerland., Hahn M; Department of Dermatology, Eberhard Karls University of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany., Aebischer V; Department of Dermatology, Eberhard Karls University of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany., Seitz CM; Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University of Tuebingen, Tuebingen, Germany., Schroeder C; Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tuebingen, Tuebingen, Germany., Liebmann A; Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tuebingen, Tuebingen, Germany., Abele M; Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University of Tuebingen, Tuebingen, Germany., Wild H; Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University of Tuebingen, Tuebingen, Germany., Bien E; Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Gdansk, Poland., Kunc M; Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland., Schneider DT; Clinic of Pediatrics, Dortmund Municipal Hospital, University Witten/Herdecke, Dortmund, Germany., Cuk K; BioNTech SE, Mainz, Germany., Büttel I; BioNTech SE, Mainz, Germany., Flemmig C; BioNTech SE, Mainz, Germany., Peters M; BioNTech SE, Mainz, Germany., Laible M; BioNTech SE, Mainz, Germany., Brück P; BioNTech SE, Mainz, Germany., Türeci Ö; BioNTech SE, Mainz, Germany., Sahin U; BioNTech SE, Mainz, Germany., Flatz L; Department of Dermatology, Eberhard Karls University of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.; Institute for Immunobiology, Kantonsspital St Gallen, St Gallen, Switzerland.; Department of Dermatology, Venereology, and Allergology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland., Brecht IB; Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
Jazyk: angličtina
Zdroj: Virchows Archiv : an international journal of pathology [Virchows Arch] 2024 Aug; Vol. 485 (2), pp. 335-346. Date of Electronic Publication: 2024 Jun 18.
DOI: 10.1007/s00428-024-03846-0
Abstrakt: Tumor-associated antigens (TAAs) are potential targets for T cell-based immunotherapy approaches in cutaneous melanoma. BNT111, an investigational lipoplex-formulated mRNA-based therapeutic cancer vaccine encoding melanoma TAAs NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, is undergoing clinical testing in adults. Expression of these TAAs in pediatric melanoma is unclear but is a prerequisite for feasibility of this treatment approach in children with melanoma. Our main objective was to characterize expression of those TAAs in pediatric melanomas compared to control cohorts. In this retrospective case control study, protein and transcript expression of NY-ESO-1, tyrosinase, MAGE-A3, and TPTE were analyzed in a cohort of 25 pediatric melanomas, 31 melanomas of young adults, 29 adult melanomas, and 30 benign melanocytic nevi in children using immunohistochemical staining and digital pathology (QuPath) and reverse transcription quantitative PCR. Based on IHC analysis, pediatric melanomas expressed tyrosinase (100.0%), TPTE (44.0%), MAGE-A3 (12.0%), and NY-ESO-1 (8.0%). Young adult melanomas expressed tyrosinase (96.8%), NY-ESO-1 (19.4%), MAGE-A3 (19.4%), and TPTE (3.2%). Adult melanomas expressed tyrosinase (86.2%), MAGE-A3 (75.9%), NY-ESO-1 (48.3%), and TPTE (48.3%). Childhood melanocytic nevi only expressed tyrosinase (93.3%). Expression prevalence of individual TAAs did not differ between subtypes of pediatric melanoma, and no association with prognosis was found. All four TAAs were expressed in pediatric melanoma, albeit NY-ESO-1 and MAGE-A3 to a lesser extent than in adult melanoma. These data support the possibility of investigating vaccines targeting these TAAs for the treatment of pediatric melanoma.
(© 2024. The Author(s).)
Databáze: MEDLINE
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