title: Nanobodies against surface biomarkers enable the analysis of tumor genetic heterogeneity in uveal melanoma patient-derived xenografts.
abstract: Monoclonal antibodies specific for biomarkers expressed on the surface of uveal melanoma (UM) cells would simplify the immune capture and genomic characterization of heterogeneous tumor cells originated from patient-derived xenografts (PDXs). Antibodies against four independent tumor antigens were isolated by panning a nanobody synthetic library. Such antibodies enabled flow cytometry-based sorting of distinct cell subpopulations from UM PDXs and to analyze their genomic features. The complexity and specificity of the biochemical and genomic biomarker combinations mirrored the UM tumor polyclonality. The data showed that MUC18 is highly and universally displayed on the surface of UM cells with different genetic background and consequently represents a reliable pan-biomarker for their identification and purification. In contrast, the other three biomarkers were detected in very variable combinations in UM PDX cells. The availability of the identified nanobodies will be instrumental in developing clone-specific drug evaluation and rational clinical strategies based on accurate genomic profiling.
authors.affiliation: Tumor Target and Therapeutic Antibody - Identification Platform (TAb-IP), Paris Cedex 05, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Crépin
authors.affiliation: Translational Research Department, Institut Curie, PSL Research University, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Gentien
authors.affiliation: Translational Research Department, Institut Curie, PSL Research University, Paris, France.
authors.forename: Angeline
authors.initials: A
authors.lastname: Duché
authors.affiliation: Translational Research Department, Institut Curie, PSL Research University, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Rapinat
authors.affiliation: Translational Research Department, Institut Curie, PSL Research University, Paris, France.
authors.forename: Cecile
authors.initials: C
authors.lastname: Reyes
authors.affiliation: Translational Research Department, Institut Curie, PSL Research University, Paris, France.
authors.forename: Fariba
authors.initials: F
authors.lastname: Némati
authors.affiliation: Translational Research Department, Institut Curie, PSL Research University, Paris, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Massonnet
authors.affiliation: Translational Research Department, Institut Curie, PSL Research University, Paris, France.|Medical Oncology Department, Institut Curie, Paris Cedex 05, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Decaudin
authors.affiliation: Tumor Target and Therapeutic Antibody - Identification Platform (TAb-IP), Paris Cedex 05, France.|Institut Curie, PSL Research University, Paris Cedex 05, France.
authors.forename: Selma
authors.initials: S
authors.lastname: Djender
authors.affiliation: Translational Research Department, Institut Curie, PSL Research University, Paris, France.|Institut Curie, PSL Research University, Paris Cedex 05, France.|UMR144, Institut Curie, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Moutel
authors.affiliation: Tumor Target and Therapeutic Antibody - Identification Platform (TAb-IP), Paris Cedex 05, France.
authors.forename: Klervi
authors.initials: K
authors.lastname: Desrumeaux
authors.affiliation: Department of Surgical Oncology, Institut Curie, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cassoux
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Piperno-Neumann
authors.affiliation: Institut Curie, PSL Research University, Paris Cedex 05, France.|INSERM Unit 932, Paris cedex 05, France.|SIRIC INCa-DGOS-4654, Paris, France.|CIC IGR Curie 1428, Paris, France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amigorena
authors.affiliation: Tumor Target and Therapeutic Antibody - Identification Platform (TAb-IP), Paris Cedex 05, France.|Institut Curie, PSL Research University, Paris Cedex 05, France.|UMR144, Institut Curie, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Perez
authors.affiliation: Translational Research Department, Institut Curie, PSL Research University, Paris, France.
authors.forename: Sergio
authors.initials: S
authors.lastname: Roman-Roman
authors.affiliation: Tumor Target and Therapeutic Antibody - Identification Platform (TAb-IP), Paris Cedex 05, France.|SIRIC INCa-DGOS-4654, Paris, France.|CIC IGR Curie 1428, Paris, France.|Department of Biomedical Sciences and Engineering, University of Nova Gorica (UNG), Vipava, Slovenia.
authors.forename: Ario
authors.identifier: 0000-0001-7729-819X
authors.initials: A
authors.lastname: de Marco
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D018740:Genetic Heterogeneity; D064593:Heterografts; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism*; D061905:Single-Domain Antibodies / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D000098943:Uveal Melanoma
chemical_list: D014408:Biomarkers, Tumor; D061905:Single-Domain Antibodies
keywords: MUC18; membrane surface biomarkers; nanobodies; panning; patient-derived xenografts; tumor polyclonality; uveal melanoma