Nanobodies against surface biomarkers enable the analysis of tumor genetic heterogeneity in uveal melanoma Patient Derived Xenografts
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 sub-populations 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 at 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
2017
2017-04-19 12:54:14
1033
nanobodies, uveal melanoma, patient derived xenografts, MUC18, membrane surface biomarkers, panning, tumor polyclonality
r6
Ronan
Crepin
70
David
Gentien
70
Angeline
Duche
70
Audrey
Rapinat
70
Cecile
Reyes
70
Fariba
Nemati
70
Gerald
Massonnet
70
Didier
Deacaudin
70
Selma
Djander
70
Sandrine
Moutel
70
Klervi Even
Desrumeaux
70
Nathalie
Cassoux
70
Sophie
Piperno-Neumann
70
Sebastian
Amigorena
70
Franck
Perez
70
Sergio
Roman-Roman
70
Ario
De Marco
70
COBISS_ID
3
4768763
DOI
15
10.1111/pcmr.12577
NUK URN
18
URN:SI:UNG:REP:TFTBEVVZ
FinalPDF.pdf
1168494
Predstavitvena datoteka
2017-04-19 12:54:28