Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation

Atanackovic, Djordje; Arfsten, Julia; Cao, Yanran; Gnjatic, Sacha; Schnieders, Frank; Bartels, Katrin; Schilling, Georgia; Faltz, Christiane; Wolschke, Christine; Dierlamm, Judith; Ritter, Gerd; Eiermann, Thomas; Hossfeld, Dieter K.; Zander, Axel R.; Jungbluth, Achim A.; Old, Lloyd J.; Bokemeyer, Carsten; Kröger, Nicolaus

doi:10.1182/blood-2006-04-014480

Cited by 151 publications

(153 citation statements)

References 47 publications

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“…CTA expression in myeloma has been evaluated in large patient sets but emphasis has so far been on newly diagnosed patients. 13,16,29,30 Compared to the study of Condomines et al, 16 presence of gene expression frequency differed no more than 2-fold in 73% of overlapping genes when compared to the frequencies found in newly diagnosed patients in our study. Of these, 12 are highly correlated with a difference in frequency of no more than 1.5-fold, including MAGEC1, MAGEA5 and SSX3; 61%, 26% and 3% in our study and 66%, 22% and 3% in the study of Condomines et al 16 In some cases, different probe sets belonging to the same gene may explain the difference in expression frequencies between the two studies.…”

Section: Discussionmentioning

confidence: 38%

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Duin¹,

Broyl²,

Knegt³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundIn multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens which can be classified by varying expression in normal tissue: restricted to testis, expressed in testis and brain and not restricted but selectively expressed in testis. Design and MethodsEvaluation of cancer testis antigen expression was made in newly diagnosed multiple myeloma cases (HOVON-65/GMMG-HD4 trial; n=320) and in relapse cases (APEX, SUMMIT, CREST trials; n=264). Presence of expression using Affymetrix GeneChips was determined for 123 cancer testis antigens. Of these 87 had a frequency of more than 5% in the newly diagnosed and relapsed patients, and were evaluated in detail. ResultsTissue restriction was known for 58 out of 87 cancer testis antigens. A significantly lower frequency of presence calls in the relapsed compared to newly diagnosed cases was found for 3 out of 13 testis restricted genes, 2 out of 7 testis/brain restricted genes, and 17 out of 38 testis selective genes. MAGEC1, MAGEB2 and SSX1 were the most frequent testis-restricted cancer testis antigens in both data sets. Multivariate analysis demonstrated that presence of MAGEA6 and CDCA1 were clearly associated with shorter progression free survival, and presence of MAGEA9 with shorter overall survival in the set of newly diagnosed cases. In the set of relapse cases, presence of CTAG2 was associated with shorter progression free survival and presence of SSX1 with shorter overall survival. ConclusionsRelapsed multiple myeloma reveals extensive cancer testis antigen expression. Cancer testis antigens are confirmed as useful prognostic markers in newly diagnosed multiple myeloma patients and in relapsed multiple myeloma patients.The HOVON-65/GMMG-HD4 trial is registered under Dutch trial register n. respectively.

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Section: Discussionmentioning

confidence: 38%

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Duin¹,

Broyl²,

Knegt³

et al. 2011

Haematologica

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“…In an allogenic transplantation setting, Atanackovic et al recently showed that at least four CT Ags expressed by MMC were immunogenic in vivo. Indeed in nine of 35 patients, an allograft resulted in the emergence of anti-SSX2, anti-MAGE-A3, and/or anti-NY-ESO-1 Abs in recipients' sera (59). In the same study, a humoral response against CT Ags was detected in the serum of only one patient of 22 treated with HDC and ABSCT.…”

Section: Discussionmentioning

confidence: 81%

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Condomines

Hose

Raynaud

et al. 2007

The Journal of Immunology

108

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Cancer-testis (CT) Ags are expressed in testis and malignant tumors but rarely in nongametogenic tissues. Due to this pattern, they represent attractive targets for cancer vaccination approaches. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in multiple myeloma (MM); 2) to assess the prognosis value of CT gene expression; and 3) to provide selection strategies for CT Ags in clinical vaccination trials. We report the expression pattern of CT genes in purified MM cells (MMC) of 64 patients with newly diagnosed MM and12 patients with monoclonal gammopathy of unknown significance, in normal plasma cell and B cell samples, and in 20 MMC lines. Of the 46 CT genes interrogated by the Affymetrix HG-U133 set arrays, 35 are expressed in the MMC of at least one patient. Of these, 25 are located on chromosome X. The expression of six CT genes is associated with a shorter event-free survival. The MMC of 98% of the patients express at least one CT gene, 86% at least two, and 70% at least three CT genes. By using a set of 10 CT genes including KM-HN-1, MAGE-C1, MAGE-A3/6/12, MAGE-A5, MORC, DDX43, SPACA3, SSX-4, GAGE-1–8, and MAGE-C2, a combination of at least three CT genes—desirable for circumventing tumor escape mechanisms—is obtained in the MMC of 67% of the patients. Provided that the immunogenicity of the products of these 10 CT genes is confirmed, gene expression profiling could be useful in identifying which CT Ags could be used to vaccinate a given patient.

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“…First, we selected 20 CT genes characterized by a strictly testis-specific expression and absence from any other healthy tissues as demonstrated in our previous studies [17][18][19]. The expression of these genes was then analyzed in 10 untreated AML cell lines by RT-PCR.…”

Section: Aml Cell Lines Show a Scarce Constitutive Expression Of Ctamentioning

confidence: 99%

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

et al. 2011

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Cancer-testis antigens (CTA) represent attractive targets for tumor immunotherapy. However, a broad picture of CTA expression in acute myeloid leukemia (AML) is missing. CTA expression was analyzed in normal bone marrow (BM) as well as in AML cell lines before and after treatment with demethylating agents and/or histone acetylase inhibitors. Presence of selected CTA with a strictly tumor-restricted expression was then determined in samples of patients with AML before and after demethylating therapy. Screening AML cell lines for the expression of 20 CTA, we identified six genes (MAGE-A3, PRAME, ROPN1, SCP-1, SLLP1, and SPO11) with an AML-restricted expression. Analyzing the expression of these CTA in blast-containing samples from AML patients (N 5 64), we found all samples to be negative for MAGE-A3 and SPO11 while a minority of patients expressed ROPN1 (1.6%), SCP-1 (3.1%), or SLLP1 (9.4%). The only CTA expressed in substantial proportion of patients (53.1%) was PRAME. Following demethylating treatment with 5 0 -aza-2 0 -deoxycytidine, we observed an increased or de novo expression of CTA, in particular of SSX-2, in AML cell lines. In AML patients, we detected increased expression of PRAME and induction of SSX-2 after demethylating therapy with 5-azacytidine. With the exception of PRAME, CTA are mostly absent from AML blasts. However, demethylating treatment induces strong expression of CTA, particularly of SSX-2, in vitro and in vivo. Therefore, we propose that CTA-specific immunotherapy for AML should preferentially target PRAME and/or should be combined with the application of demethylating agents opening the perspective for alternative targets like CTA SSX-2. Am. J. Hematol. 86:918-922, 2011. V

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Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation

Cited by 151 publications

References 47 publications

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

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