Frequency of expression and generation of T-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial
Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results Expression by GEP is found fo...
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| Hauptverfasser: | , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2017
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| In: |
OncoTarget
Year: 2017, Jahrgang: 8, Heft: 49, Pages: 84847-84862 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.11215 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.18632/oncotarget.11215 Verlag, kostenfrei, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689578/ 
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| Verfasserangaben: | Michael Schmitt, Angela G. Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D. Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger and Dirk Hose |
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| 245 | 1 | 0 | |a Frequency of expression and generation of T-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial |c Michael Schmitt, Angela G. Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D. Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger and Dirk Hose |
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| 500 | |a Gesehen am 12.06.2018 | ||
| 520 | |a Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing. T-cell-activation is found in 9/26 (34.6%) of patient samples, i.e. against HM1.24 (4/24), RHAMM-R3 (3/26), RHAMM1-8 (2/14), WT-1 (1/11), NY-ESO-1/2 (1/9), and MAGE-A3 (2/8). In 7/19 T-cell activation responses, myeloma cells lack respective antigen-expression. Expression of MAGE-A3, HMMR and NY-ESO-1/2 is associated with adverse survival. Experimental design: We assessed expression of HM1.24 and the CTAs MAGE-A3, NY-ESO-1/2, WT-1 and HMMR in CD138-purified myeloma cell samples of previously untreated myeloma patients in the GMMG-MM5 multicenter-trial by gene expression profiling (GEP; n = 458) and RNA-sequencing (n = 152) as potential population regarding vaccination trials. We then validated the feasibility to generate T-cell responses (n = 72) against these antigens by IFN-γ EliSpot-assay (n = 26) related to antigen expression (n = 22). Lastly, we assessed survival impact of antigen expression in an independent cohort of 247 patients treated by high-dose therapy and autologous stem cell transplantation. Conclusions: As T-cell responses can only be raised in a subfraction of patients despite antigen expression, and the number of responses increases with more antigens used, vaccination strategies should assess patients’ antigen expression and use a “cocktail” of peptide vaccines. | ||
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