Expression of Cancer-Testis Antigens in Stem Cells: Is it a Potential Drawback or an Advantage in Cancer Immunotherapy

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.

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The use of Cancer/Testis antigens to monitor levels of circulating malignant stem cells in Multiple Myeloma.

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2019.09.304 ◽

2019 ◽

Vol 19 (10) ◽

pp. e182

Author(s):

karen Shires ◽

Kirsty Wienand

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Cancer Testis Antigens ◽

Cancer Testis

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Expression Patterns of Cancer-Testis Antigens in Human Embryonic Stem Cells and Their Cell Derivatives Indicate Lineage Tracks

Stem Cells International ◽

10.4061/2011/795239 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 27

Author(s):

Nadya Lifantseva ◽

Anna Koltsova ◽

Tatyana Krylova ◽

Tatyana Yakovleva ◽

Galina Poljanskaya ◽

...

Keyword(s):

Stem Cells ◽

Cell Lines ◽

Cancer Cell ◽

Pluripotent Stem Cells ◽

Expression Patterns ◽

Embryonic Stem ◽

Cancer Cell Lines ◽

Cancer Testis Antigens ◽

Hes Cells ◽

Cancer Testis

Pluripotent stem cells can differentiate into various lineages but undergo genetic and epigenetic changes during long-term cultivation and, therefore, require regular monitoring. The expression patterns of cancer-testis antigens (CTAs) MAGE-A2, -A3, -A4, -A6, -A8, -B2, and GAGE were examined in undifferentiated human embryonic stem (hES) cells, their differentiated derivatives, teratocarcinoma (hEC) cells, and cancer cell lines of neuroectodermal and mesodermal origin. Undifferentiated hES cells and embryoid body cells expressed MAGE-A3, -A6, -A4, -A8, and GAGEs while later differentiated derivatives expressed only MAGE-A8 or MAGE-A4. Likewise, mouse pluripotent stem cells also express CTAs of Magea but not Mageb family. Despite similarity of the hES and hEC cell expression patterns, MAGE-A2 and MAGE-B2 were detected only in hEC cells but not in hES cells. Moreover, our analysis has shown that CTAs are aberrantly expressed in cancer cell lines and display low tissue specificity. The identification of CTA expression patterns in pluripotent stem cells and their derivatives may be useful for isolation of abnormally CTA-expressing cells to improve the safety of stem-cell based therapy.

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Demethylation of Cancer/Testis Antigens and CpG ODN Stimulation Enhance Dendritic Cell and Cytotoxic T Lymphocyte Function in a Mouse Mammary Model

BioMed Research International ◽

10.1155/2013/196894 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Jun-Zhong Sun ◽

Lei Gao ◽

Li Gao ◽

Wei Wang ◽

Nan Du ◽

...

Keyword(s):

Cancer Immunotherapy ◽

Target Cells ◽

Cytotoxic Lymphocytes ◽

Lymphocyte Function ◽

Cpg Odn ◽

Cancer Testis Antigens ◽

Cpg Oligodeoxynucleotide ◽

Immune Adjuvant ◽

Cancer Testis

Background. Cancer/testis antigens (CTAs) are ideal targets for cancer immunotherapy in virtue of their restricted expression profile in normal tissues. However, CTA-targeted immunotherapy has been rather disappointing clinical setting for CTAs are downregulated by cytosine-phosphate-guanosine (CpG) methylation in their promoter regions, so that tumor cells have low immunogenicity.Methods. We reinduced mouse CTA P1A through demethylation process and generated P1A-specific cytotoxic lymphocytes (CTLs) by immunizing BALB/c (H-2d) mice with dendritic cells pulsed with a P1A-specific peptide and CpG oligodeoxynucleotide (ODN) immune adjuvant.Results. We found that demethylation and CpG ODN immune adjuvant stimulation facilitated DC maturation and enhanced the allogenic capacity of P1A-specific CTLs against target cells bothin vitroandin vivo.Conclusions. Our results suggested that CTA induction and immune adjuvant stimulation is a feasible strategy in cancer immunotherapy.

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