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Nanobodies against surface biomarkers enable the analysis of tumor genetic heterogeneity in uveal melanoma patient‐derived xenografts |
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| Authors: | Angeline Duché Audrey Rapinat Cecile Reyes Fariba Némati Gérald Massonnet Didier Decaudin Selma Djender Sandrine Moutel Klervi Desrumeaux Nathalie Cassoux Sophie Piperno‐Neumann Sebastian Amigorena Franck Perez Sergio Roman‐Roman Ario de Marco |
| Institution: | 1. Translational Research Department, Institut Curie, PSL Research University, Paris, France;2. Medical Oncology Department, Institut Curie, Paris Cedex 05, France;3. Tumor Target and Therapeutic Antibody ‐ Identification Platform (TAb‐IP), Paris Cedex 05, France;4. Institut Curie, PSL Research University, Paris Cedex 05, France;5. UMR144, Institut Curie, Paris, France;6. Department of Surgical Oncology, Institut Curie, Paris, France;7. Department of Medical Oncology, Institut Curie, Paris, France;8. INSERM Unit 932, Paris cedex 05, France;9. SIRIC INCa‐DGOS‐4654, Paris, France;10. CIC IGR Curie 1428, Paris, France;11. Department of Biomedical Sciences and Engineering, University of Nova Gorica (UNG), Vipava, Slovenia |
| 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. |
| Keywords: | nanobodies uveal melanoma patient‐derived xenografts MUC18 membrane surface biomarkers panning tumor polyclonality |