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

Abstract

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.

Human MageB2 Protein Expression Enhances E2F Transcriptional Activity, Cell Proliferation, and Resistance to Ribotoxic Stress

“…In addition, MageB2 overexpression showed growth-promoting effect in a transformed oral keratinocyte cell line (23). Even though human MageB2 expression is found in a variety of human cancers, such as lung carcinoma (22), head and neck squamous cell carcinoma (23), multiple myeloma (24), and renal cell carcinoma (25), its function in tumor cells is mostly unknown.…”

MHC class II/ESO tetramer-based generation of in vitro primed anti-tumor T-helper lines for adoptive cell therapy of cancer

“…For the assessment of their functional avidity, ESO-specific polyclonal T H lines (10 4 ) were incubated with JBUSH cells (10 4 ) in the presence of serial dilutions of peptide ESO 119-143 (1 mM) or a control irrelevant peptide (ESO [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] ), and IFN-g was assessed in 24-h culture supernatants by ELISA (Invitrogen). For the assessment of the reactivity of ESO-specific lines to naturally processed full-length ESO, Figure S1).…”

“…melanoma, ovarian cancer) 3,4 and hematologic (e.g. multiple myeloma (MM) adult T-cell leukemia/lymphoma (ATLL)) [5][6][7][8][9] tumors, and represents an attractive target for cancer immunotherapy. Different ESO-based immunotherapeutic approaches are under development, including vaccines 10,11 and passive adoptive cell transfer (ACT) therapy using adoptively transferred ESO-specific T cells, which is particularly attractive for the treatment of patients with recurrent disease.…”

Expression of Cancer-Testis Genes Prame, Ny-Eso1, Gage1, Mage A3, Mage A6, Mage A12, Ssx1, Sllp1, Pasd1 in Patients With Multiple Myeloma, Their Influence on Overall Survival and Relapse Rate

“…Ранее продемонстрированно, что экспрессия генов семейства MAGE, NY-ESO1, SSX1, PASD1 прямо кор-релирует с более поздней стадией болезни, неблаго-приятным прогнозом, более короткими сроками БРВ [29,30]. Результаты, полученные нами, подтверждают эти данные.…”