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Schmitt, Michael [Author]; Hückelhoven-Krauss, Angela [Author]; Hundemer, Michael [Author]; Schmitt, Anita [Author]; Lipp, Susanne [Author]; Emde-Rajaratnam, Martina [Author]; Salwender, Hans [Author]; Hänel, Mathias [Author]; Weisel, Katja [Author]; Bertsch, Uta [Author]; Dürig, Jan [Author]; Ho, Anthony Dick [Author]; Blau, Igor-Wolfgang [Author]; Goldschmidt, Hartmut [Author]; Seckinger, Anja [Author]; Hose, Dirk [Author]

Frequency of expression and generation of T-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial

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  • Media type: E-Article
  • Title: Frequency of expression and generation of T-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial
  • Contributor: Schmitt, Michael [Author]; Hückelhoven-Krauss, Angela [Author]; Hundemer, Michael [Author]; Schmitt, Anita [Author]; Lipp, Susanne [Author]; Emde-Rajaratnam, Martina [Author]; Salwender, Hans [Author]; Hänel, Mathias [Author]; Weisel, Katja [Author]; Bertsch, Uta [Author]; Dürig, Jan [Author]; Ho, Anthony Dick [Author]; Blau, Igor-Wolfgang [Author]; Goldschmidt, Hartmut [Author]; Seckinger, Anja [Author]; Hose, Dirk [Author]
  • Published: 2017
  • Published in: OncoTarget ; 8(2017), 49, Seite 84847-84862
  • Language: English
  • DOI: 10.18632/oncotarget.11215
  • Identifier:
  • Origination:
  • Footnote: Published: August 11, 2016
  • Description: 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.
  • Access State: Open Access