Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma
Despite the recent introduction of next-generation immunotherapeutic agents, multiple myeloma (MM) remains incurable. New strategies targeting MM-specific antigens may result in a more effective therapy by preventing antigen escape, clonal evolution, and tumor resistance. In this work, we adapted an...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-07-01
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| Series: | HemaSphere |
| Online Access: | http://journals.lww.com/10.1097/HS9.0000000000000901 |
| _version_ | 1797225358742781952 |
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| author | Margaux Lejeune Murat Cem Köse Mégane Jassin Marie-Jia Gou Amaury Herbet Elodie Duray Gaël Cobraiville Jacques Foguenne Didier Boquet André Gothot Yves Beguin Marianne Fillet Jo Caers |
| author_facet | Margaux Lejeune Murat Cem Köse Mégane Jassin Marie-Jia Gou Amaury Herbet Elodie Duray Gaël Cobraiville Jacques Foguenne Didier Boquet André Gothot Yves Beguin Marianne Fillet Jo Caers |
| author_sort | Margaux Lejeune |
| collection | DOAJ |
| description | Despite the recent introduction of next-generation immunotherapeutic agents, multiple myeloma (MM) remains incurable. New strategies targeting MM-specific antigens may result in a more effective therapy by preventing antigen escape, clonal evolution, and tumor resistance. In this work, we adapted an algorithm that integrates proteomic and transcriptomic results of myeloma cells to identify new antigens and possible antigen combinations. We performed cell surface proteomics on 6 myeloma cell lines based and combined these results with gene expression studies. Our algorithm identified 209 overexpressed surface proteins from which 23 proteins could be selected for combinatorial pairing. Flow cytometry analysis of 20 primary samples confirmed the expression of FCRL5, BCMA, and ICAM2 in all samples and IL6R, endothelin receptor B (ETB), and SLCO5A1 in >60% of myeloma cases. Analyzing possible combinations, we found 6 combinatorial pairs that can target myeloma cells and avoid toxicity on other organs. In addition, our studies identified ETB as a tumor-associated antigen that is overexpressed on myeloma cells. This antigen can be targeted with a new monoclonal antibody RB49 that recognizes an epitope located in a region that becomes highly accessible after activation of ETB by its ligand. In conclusion, our algorithm identified several candidate antigens that can be used for either single-antigen targeting approaches or for combinatorial targeting in new immunotherapeutic approaches in MM. |
| first_indexed | 2024-03-13T01:05:02Z |
| format | Article |
| id | doaj.art-941162fc8eb943a5ac5f70af1a269293 |
| institution | Directory Open Access Journal |
| issn | 2572-9241 |
| language | English |
| last_indexed | 2024-04-24T14:07:45Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj.art-941162fc8eb943a5ac5f70af1a2692932024-04-03T09:47:40ZengWileyHemaSphere2572-92412023-07-0177e90110.1097/HS9.0000000000000901202307000-00002Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple MyelomaMargaux Lejeune0Murat Cem Köse1Mégane Jassin2Marie-Jia Gou3Amaury Herbet4Elodie Duray5Gaël Cobraiville6Jacques Foguenne7Didier Boquet8André Gothot9Yves Beguin10Marianne Fillet11Jo Caers121 Laboratory of Hematology, GIGA I3, University of Liège, Belgium1 Laboratory of Hematology, GIGA I3, University of Liège, Belgium1 Laboratory of Hematology, GIGA I3, University of Liège, Belgium2 Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium3 Université Paris-Saclay, CEA, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France1 Laboratory of Hematology, GIGA I3, University of Liège, Belgium2 Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium4 Department of Hematobiology and Immunohematology, CHU de Liège, Belgium3 Université Paris-Saclay, CEA, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France4 Department of Hematobiology and Immunohematology, CHU de Liège, Belgium1 Laboratory of Hematology, GIGA I3, University of Liège, Belgium2 Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium1 Laboratory of Hematology, GIGA I3, University of Liège, BelgiumDespite the recent introduction of next-generation immunotherapeutic agents, multiple myeloma (MM) remains incurable. New strategies targeting MM-specific antigens may result in a more effective therapy by preventing antigen escape, clonal evolution, and tumor resistance. In this work, we adapted an algorithm that integrates proteomic and transcriptomic results of myeloma cells to identify new antigens and possible antigen combinations. We performed cell surface proteomics on 6 myeloma cell lines based and combined these results with gene expression studies. Our algorithm identified 209 overexpressed surface proteins from which 23 proteins could be selected for combinatorial pairing. Flow cytometry analysis of 20 primary samples confirmed the expression of FCRL5, BCMA, and ICAM2 in all samples and IL6R, endothelin receptor B (ETB), and SLCO5A1 in >60% of myeloma cases. Analyzing possible combinations, we found 6 combinatorial pairs that can target myeloma cells and avoid toxicity on other organs. In addition, our studies identified ETB as a tumor-associated antigen that is overexpressed on myeloma cells. This antigen can be targeted with a new monoclonal antibody RB49 that recognizes an epitope located in a region that becomes highly accessible after activation of ETB by its ligand. In conclusion, our algorithm identified several candidate antigens that can be used for either single-antigen targeting approaches or for combinatorial targeting in new immunotherapeutic approaches in MM.http://journals.lww.com/10.1097/HS9.0000000000000901 |
| spellingShingle | Margaux Lejeune Murat Cem Köse Mégane Jassin Marie-Jia Gou Amaury Herbet Elodie Duray Gaël Cobraiville Jacques Foguenne Didier Boquet André Gothot Yves Beguin Marianne Fillet Jo Caers Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma HemaSphere |
| title | Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma |
| title_full | Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma |
| title_fullStr | Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma |
| title_full_unstemmed | Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma |
| title_short | Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma |
| title_sort | integrative analysis of proteomics and transcriptomics reveals endothelin receptor b as novel single target and identifies new combinatorial targets for multiple myeloma |
| url | http://journals.lww.com/10.1097/HS9.0000000000000901 |
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