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

Standard

Frequency of expression and generation of T-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial. / Schmitt, Michael; Hückelhoven, Angela G; Hundemer, Michael; Schmitt, Anita; Lipp, Susanne; Emde, Martina; Salwender, Hans; Hänel, Mathias; Weisel, Katja; Bertsch, Uta; Dürig, Jan; Ho, Anthony D; Blau, Igor Wolfgang; Goldschmidt, Hartmut; Seckinger, Anja; Hose, Dirk.

in: ONCOTARGET, Jahrgang 8, Nr. 49, 17.10.2017, S. 84847-84862.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Schmitt, M, Hückelhoven, AG, Hundemer, M, Schmitt, A, Lipp, S, Emde, M, Salwender, H, Hänel, M, Weisel, K, Bertsch, U, Dürig, J, Ho, AD, Blau, IW, Goldschmidt, H, Seckinger, A & Hose, D 2017, 'Frequency of expression and generation of T-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial', ONCOTARGET, Jg. 8, Nr. 49, S. 84847-84862. https://doi.org/10.18632/oncotarget.11215

APA

Schmitt, M., Hückelhoven, A. G., Hundemer, M., Schmitt, A., Lipp, S., Emde, M., Salwender, H., Hänel, M., Weisel, K., Bertsch, U., Dürig, J., Ho, A. D., Blau, I. W., Goldschmidt, H., Seckinger, A., & Hose, D. (2017). Frequency of expression and generation of T-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial. ONCOTARGET, 8(49), 84847-84862. https://doi.org/10.18632/oncotarget.11215

Vancouver

Schmitt M, Hückelhoven AG, Hundemer M, Schmitt A, Lipp S, Emde M et al. Frequency of expression and generation of T-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial. ONCOTARGET. 2017 Okt 17;8(49):84847-84862. https://doi.org/10.18632/oncotarget.11215

Bibtex

@article{4eb4156570c647d680280a2b16df93a3,
title = "Frequency of expression and generation of T-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial",
abstract = "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.",
keywords = "Journal Article",
author = "Michael Schmitt and H{\"u}ckelhoven, {Angela G} and Michael Hundemer and Anita Schmitt and Susanne Lipp and Martina Emde and Hans Salwender and Mathias H{\"a}nel and Katja Weisel and Uta Bertsch and Jan D{\"u}rig and Ho, {Anthony D} and Blau, {Igor Wolfgang} and Hartmut Goldschmidt and Anja Seckinger and Dirk Hose",
year = "2017",
month = oct,
day = "17",
doi = "10.18632/oncotarget.11215",
language = "English",
volume = "8",
pages = "84847--84862",
journal = "ONCOTARGET",
issn = "1949-2553",
publisher = "IMPACT JOURNALS LLC",
number = "49",

}

RIS

TY - JOUR

T1 - Frequency of expression and generation of T-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial

AU - Schmitt, Michael

AU - Hückelhoven, Angela G

AU - Hundemer, Michael

AU - Schmitt, Anita

AU - Lipp, Susanne

AU - Emde, Martina

AU - Salwender, Hans

AU - Hänel, Mathias

AU - Weisel, Katja

AU - Bertsch, Uta

AU - Dürig, Jan

AU - Ho, Anthony D

AU - Blau, Igor Wolfgang

AU - Goldschmidt, Hartmut

AU - Seckinger, Anja

AU - Hose, Dirk

PY - 2017/10/17

Y1 - 2017/10/17

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.18632/oncotarget.11215

DO - 10.18632/oncotarget.11215

M3 - SCORING: Journal article

C2 - 29156688

VL - 8

SP - 84847

EP - 84862

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 49

ER -