The cancer-testis antigens CT7 (MAGE-C1) and MAGE-A3/6 are commonly expressed in multiple myeloma and correlate with plasma-cell proliferation

Jungbluth, Achim A.; Ely, Scott; DiLiberto, Maurizio; Niesvizky, Rubén; Williamson, Barbara; Frosina, Denise; Chen, Yao‐Tseng; Bhardwaj, Nina; Chen‐Kiang, Selina; Old, Lloyd J.; Cho, Hearn Jay

doi:10.1182/blood-2004-12-4931

Cited by 172 publications

(175 citation statements)

References 39 publications

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“…In addition, CT-X gene expression in patients with epithelial cancers is often associated with a poor patient outcome (52)(53)(54). Our data are also in agreement with recent studies emphasizing that the MMC of patients that express MAGE-C1, MAGE-A3, and/or NY-ESO-1 had an increased proliferative activity and are obtained mainly from patients with stage III MM (32,40). These gene products might have a functional role in the pathogenesis of cancer leading to a bad evolution.…”

Section: Discussionsupporting

confidence: 91%

“…MAGE-C1 is the most frequently expressed CT gene (66%) by MMC of newly diagnosed MM-patients as previously observed in a small group of 29 patients by Dhodapkar et al (40). We also confirmed that SPACA3/SLLP1, SPANXB, and the MAGE-A, GAGE, CTAG, and SSX gene families are expressed by MMC (20,29,31,32,(41)(42)(43)(44). The CT Ag CTAG1B/ NY-ESO-1, known to be highly immunogenic (27,45,46), shows the highest median signal in MMC compared to the testis with a frequency of presence of 13% in MM patients, which is lower than the frequency observed by van Rhee et al (31).…”

Section: Discussionsupporting

confidence: 74%

“…The HMCL with a "present" Affymetrix call were stained positively with the respective anti-CT Ag Abs, unlike the HMCL with an "absent" Affymetrix call. Previous studies already showed a correlation between gene and protein expression for MAGE-A or NY-ESO-1 CT Ags in MMC (32,41). It will be necessary to further extend this protein validation for each of the 35 CT genes expressed in MMC when the specific Abs become available.…”

Section: Discussionmentioning

confidence: 89%

“…The expression of NY-ESO-1 has been correlated with a poor prognosis and its frequency is increased in patients displaying genetic abnormalities determined by conventional cytogenetic analyses (31). CT7/MAGE-C1 and MAGE-A3/6 protein expression correlated with elevated MMC proliferation (32). A recent study (28) reported the presence of functional CD8 T lymphocytes against NY-ESO-1, LAGE-1, and MAGE-A1,-A2, -A3, and -A4 in the peripheral blood of MM patients.…”

Section: Ultiple Myeloma (Mm) 3 Is a B Cell Neoplasia Charac-mentioning

confidence: 99%

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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

109

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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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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 89%

Section: Ultiple Myeloma (Mm) 3 Is a B Cell Neoplasia Charac-mentioning

confidence: 99%

See 2 more Smart Citations

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

109

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“…The only normal adult human cells expressing MAGE-A3 are male germ cells and trophoblast cells of the placenta; however, in these cells the lack of classical class I (A, B and C) human leukocyte antigen expression should prevent antigen presentation, excluding the potential risk of developing an immune-related toxicity upon MAGE-A3 immunotherapy (Jungbluth et al, 2005;Scanlan et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Non‐clinical safety evaluation of single and repeated intramuscular administrations of MAGE‐A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys

Destexhe

Grosdidier

Baudson

et al. 2014

J of Applied Toxicology

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The MAGE-A3 recombinant protein combined with AS15 immunostimulant (MAGE-A3 Cancer Immunotherapeutic) is under development by GlaxoSmithKline for the treatment of lung cancer and melanoma. We performed non-clinical safety studies evaluating potential local and systemic toxic effects induced by MAGE-A3 Cancer Immunotherapeutic in rabbits (study 1) and cynomolgus monkeys (study 2). Animals were allocated to two groups to receive a single (rabbits) or 25 repeated (every 2 weeks) injections (monkeys) of MAGE-A3 Cancer Immunotherapeutic (treatment groups) or saline (control groups). All rabbits were sacrificed 3 days post-injection and monkeys 3 days following last injection (3/5 per gender per group) or after a 3-month treatment-free period (2/5 per gender per group). Local and systemic reactions and MAGE-A3-specific immune responses (monkeys) were assessed. Macroscopic and microscopic (for rabbits, injection site only) post-mortem examinations were performed on all animals. No systemic toxicity or unscheduled mortalities were recorded. Single (rabbits) and repeated (monkeys; up to four times at the same site) injections were well tolerated. Following five to seven repeated injections, limb circumferences increased up to 26% (5 h post-injection), but returned to normal after 1-8 days. Three days after the last injection, enlargements of iliac, popliteal, axillary and inguinal lymph nodes, and increased incidence or severity of mononuclear inflammatory cell infiltrates was observed in injected muscles of treated monkeys. No treatment-related macroscopic findings were recorded after the treatment-free period. MAGE-A3-specific antibody and T-cell responses were raised in all treated monkeys, confirming test item exposure. Single or repeated intramuscular injections of MAGE-A3 Cancer Immunotherapeutic were well tolerated in rabbits and monkeys.

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Cancer Testis Antigens

Cebon

Caballero

John

et al. 2009

Tumor‐Associated Antigens

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The cancer-testis antigens CT7 (MAGE-C1) and MAGE-A3/6 are commonly expressed in multiple myeloma and correlate with plasma-cell proliferation

Cited by 172 publications

References 39 publications

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

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

Non‐clinical safety evaluation of single and repeated intramuscular administrations of MAGE‐A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys

Cancer Testis Antigens

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