scholarly journals Cancer-testis antigen MAGE-C1/ CT7 in multiple myeloma: literature review

2020 ◽  
Vol 15 (4) ◽  
pp. 29-37
Author(s):  
E. A. Makunina
Keyword(s):  
Multiple Myeloma ◽  
Germ Cells ◽  
Gene Families ◽  
Transformation Process ◽  
Cancer Testis Antigen ◽  
Hematological Diseases ◽  
Cancer Testis Antigens ◽  
Disease Prognosis ◽  
Tumor Transformation ◽  
Cancer Testis

Group of tumor-associated antigens, which is normally expressed in placental cells and testicular germ cells, is called cancer-testis antigens. To date, more than 40 gene families have been identified that encode cancer-testis antigens, and their expression has been studied in many types of malignant diseases. It is assumed that the expression of cancer-testis antigens can contribute to the development of the tumor transformation process, including hematological diseases. Of particular interest in the pathogenesis of multiple myeloma is the MAGE-C1/CT7 antigen, the expression of which is most often detected in this case. According to data published by various authors, the expression of MAGEC1 in multiple myeloma can be considered as an additional marker of a poor disease prognosis, represent the effectiveness of chemotherapy approaches, and, possibly, be an earlier predictor of relapse or progression.

scholarly journals P07.02 High-affinity TCRs specific for cancer testis antigens as a therapy for multiple myeloma and solid tumors

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A49.1-A49
Author(s):  
MAJ de Rooij ◽  
DM van der Steen ◽  
D Remst ◽  
A Wouters ◽  
M van der Meent ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
Tumor Cell ◽  
Cross Reactivity ◽  
Tumor Cell Lines ◽  
High Affinity ◽  
Cancer Testis Antigens ◽  
Efficient Recognition ◽  
Cancer Testis

BackgroundCancer Testis Antigens (CTAs) are highly expressed in multiple different tumor types, but silent in normal tissue, except the testis. This tumor-restricted expression pattern makes them an ideal target for adoptive T-cell therapy. However, the responsiveness in clinical setting may be hampered because high-affinity T cells against self-antigens presented in the context of self-HLA are deleted in the thymus by negative selection. In this study, we aim to identify high-affinity T cell receptors (TCRs) specific for CTAs from the allogeneic-HLA repertoire.Materials and MethodsIn this study, HLA class I binding peptides derived from different CTA genes were identified by HLA-peptide elution experiments and subsequent mass spectrometric analysis. From the identified peptides HLA tetramers were generated to isolate peptide specific CD8+ T cells from healthy allogeneic donors. Efficacy and safety of the TCRs was determined by various different stimulation assays. The most potent TCRs were sequenced, analyzed and transduced into peripheral CD8+ and CD4+ T cells to confirm CTA specific cytokine production and cytotoxicity.ResultsMAGE and CTAG peptides were eluted from multiple myelomas, EBV-transformed lymphoblastic cells, acute myeloid leukemia and ovarium carcinomas. We selected TCRs recognizing 3 different MAGE-A1 peptides in the context of HLA-A*02:01, HLA-A*03:01 and HLA-B*07:02. Furthermore, we selected TCRs specific for MAGE-A3 in the context of HLA-B*35:01 and HLA-A*01:01; TCRs specific for MAGE-A9 in the context of HLA-A*01:01 and TCRs specific for CTAG1 in the context of HLA-A*02:01. The selected T-cell clones demonstrated efficient recognition of MAGE-A1, MAGE-A3 or CTAG1 positive multiple myeloma and solid tumor cell lines without detectable cross-reactivity.ConclusionsWe identified multiple different TCRs from the allogeneic-HLA repertoire specific for CTA genes. These TCRs demonstrate efficient recognition and killing of CTA positive multiple myeloma and solid tumor cell lines and did not show any cross-reactivity. The peptides recognized by the TCRs are presented in different HLA alleles. Since, 71% of the world population contains one of these HLA-alleles, a large percentage suffering from a MAGE or CTAG positive tumor could potentially be treated with the identified TCRs by TCR-gene therapy.Disclosure InformationM.A.J. de Rooij: None. D.M. van der Steen: None. D. Remst: None. A. Wouters: None. M. van der Meent: None. R.S. Hagedoorn: None. M.G.D. Kester: None. P.A. van Veelen: None. F.J.H. Falkenburg: None. M.H.M. Heemskerk: None.

416 Cancer-testis Antigen MAGE-C2/CT10 Promotes Proliferation and Resistance to Apoptosis in Multiple Myeloma

2012 ◽  
Vol 48 ◽  
pp. S101
Author(s):  
N. Lajmi ◽  
T. Luetkens ◽  
Y. Cao ◽  
Y. Hildebrandt ◽  
K. Bartels ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cancer Testis Antigen ◽  
Cancer Testis

scholarly journals Immunotherapy in Multiple Myeloma Using Cancer-Testis Antigens

2015 ◽  
Vol 8 (5) ◽  
Author(s):  
Soudeh Ghafouri-Frad ◽  
Mahnaz Seifi-Alan ◽  
Roshanak Shamsi ◽  
Ali Esfandiary
Keyword(s):  
Multiple Myeloma ◽  
Cancer Testis Antigens ◽  
Cancer Testis

scholarly journals The Cancer/Testis Antigens of SSX4, MAGE-A3, and CTAG2 Are Attractive Targets for Cancer Immunotherapy in Korean Patients with Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5757-5757
Author(s):  
Nu-Ri Choi ◽  
Sung-Hoon Jung ◽  
Hyun-Ju Lee ◽  
Manh-Cuong Vo ◽  
My-Dung Hoang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cancer Immunotherapy ◽  
Expression Pattern ◽  
Light Chain ◽  
Plasma Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Fold Increase ◽  
Korean Patients ◽  
Cancer Testis Antigens ◽  
Cancer Testis

Abstract Introduction: Cancer/testis antigens (CTAs) are an attractive target for cancer immunotherapy because of a tumor-restricted expression and remarkable immunogenicity. Several CTAs have been used as a source of tumor antigen in dendritic cell therapy against multiple myeloma (MM), but there was no report the CTAs in Asian patients with MM. In this study, we evaluate the expression of 10 CTAs on malignant plasma cells of bone marrow in 18 Korean patients with relapsed or refractory MM. Materials and methods: Eighteen patients with relapsed or refractory MM were classified as four categories according to paraprotein subtypes: IgG (n=7), IgA (n=5), light chain-lambda (n=3), and light chain-kappa (n=3). The expression pattern of 10 CTAs, including NY-ESO-1, SSX2, SSX4, SSX5, MAGE-A3, MAGE-C1, MAGE-C2, BAGE2, CTAG2, and SPA7, was studied by real-time quantitative polymerase chain reaction in CD138+ cells of BM mononuclear cells (MNCs) obtained from MM patients. In addition, we compared it with expression pattern of CTAs in the MNCs from healthy normal donors and the CD138- cells of BM MNCs from MM patients as controls. Results: In CD138+ cells of BM MNCs from the patients, five CTAs, including SSX2, SSX4, MAGE-A3, MAGEC2, and CTAG2, showed high frequency and overall 5.4 to 63.9 fold increase expression in the quantitative mRNA survey compared to MNCs from healthy donors and CD138- cells of BM MNCs from patients. Expression pattern of 5 CTAs was slightly different by paraprotein subtypes: IgA subtype - SSX4 (17.1 fold increase), MAGE-A3 (11.0 fold increase), and CTAG2 (5.9 fold increase); IgG subtype - CTAG2 (63.9 fold increase), SSX4 (40.2 fold increase), and MAGE-A3 (39.9 fold increase); lambda light chain subtype - CTAG2 (42.4 fold increase), SSX4 (29.0 fold increase), and MAGE-A3 (24.4 fold increase); kappa light chain subtype - SSX2 (6.4 fold increase), MAGE-C2 (6.2 fold increase), MAGE-A3 (5.4 fold increase), and SSX4 (5.4 fold increase). Conclusion: This study suggests that three CTAs, such as SSX4, MAGE-A3, and CTAG2, highly expressed on malignant plasma cells are potentially promising targets for cancer immunotherapy in Korean patients with relapsed or refractory MM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Over‐Expression of Cancer Testis Antigen Genes in Multiple Myeloma Stem Cell‐like Cells

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Jianguo Wen ◽  
Barbara Savoldo ◽  
Youli Zu ◽  
Chung‐Che Chang
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Cancer Testis Antigen ◽  
Over Expression ◽  
Cancer Testis
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