Cancer/Testis Antigen MAGE-C1/CT7: New Target for Multiple Myeloma Therapy

Carvalho, Flávio; Vettore, André Luiz; Colleoni, Gisele W. B.

doi:10.1155/2012/257695

Cited by 23 publications

(21 citation statements)

References 54 publications

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“…The most prominent antigens among this group are the cancer-testis family of antigens including MAGE [17,18], BAGE, LAGE, GAGE, and NY-ESO-1 [19–22], which in normal tissues are restricted only to the testis and placenta but can be found in MM, breast, ovarian, and head and neck cancers [23,24]. …”

Section: Classification Of Tumor Antigensmentioning

confidence: 99%

Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood and Marrow Transplantation

Zilberberg

Feinman

Korngold

2015

Biology of Blood and Marrow Transplantation

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Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient’s cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient’s existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic immunological studies for their ability to produce effective T cell responses. The first step towards this goal is the identification of targetable tumor antigens. In this review, we will highlight some of the technologies currently used to identify tumor antigens and anti-tumor T cell clones in hematological malignancies.

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Section: Classification Of Tumor Antigensmentioning

confidence: 99%

Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood and Marrow Transplantation

Zilberberg

Feinman

Korngold

2015

Biology of Blood and Marrow Transplantation

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“…170 Various studies describe the role of MAGE-C1/C17 in the proliferation, disease progression, cell adhesion, chemosensitivity and apoptosis. 171,172 So CTAs might constitute important targets for novel anti-myeloma specific therapies. Other molecules, monoclonal antibodies, particularly anti-IL-6 antibodies, 173 AE491…”

Section: New Therapies / Future Perspectives/ New Investigational Agentsmentioning

confidence: 99%

Multiple myeloma: the disease and its treatment

Gupta¹,

Pal²,

Tikoo³

2013

Int J Basic Clin Pharmacol

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Multiple myeloma represents a malignant proliferation of plasma cells derived from a single clone. The tumor, its products and the host response to it result in a number of organ dysfunctions and symptoms of bone pain, fracture, anemia, hypercalcemia, susceptibility to infection, neurologic symptoms, clotting abnormalities and manifestations of hyperviscosity. The cause of myeloma remains unexplained but it is associated with few occupations, inflammatory conditions, autoimmune illnesses, viral infections and genetic heterogeneity. Direct interaction between multiple myeloma cells and bone marrow cells activates pleiotropic signalling pathways that mediate growth, survival, migration of multiple myeloma cells and also resistance to chemotherapy. Although myeloma remains incurable, but the use of novel drugs like thalidomide, lenalidomide and bortezomib have resulted in a paradigm change in the therapy of myeloma. Their inclusion in current multiple myeloma treatment regimens have extended median overall survival especially in younger patient population. Recent advances in the molecular genetics have provided opportunities to design highly specific inhibitors of signal transduction pathways that may enhance the efficacy of standard chemotherapy drugs by reducing or altering the pathways associated with cell survival. Despite therapeutic advances, multiple myeloma ultimately relapses and remains an incurable disease. Current research goals are to further increase our knowledge, to identify additional targeted therapies, and to reduce adverse effects and improve response rate. This review focuses on recent clinical advancement in ant myeloma strategies with additional discussion dedicated to emerging drugs that may prove beneficial to patients with this disease. [Int J Basic Clin Pharmacol 2013; 2(2.000): 103-121

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“…In this study, we used immunohistochemistry to investigate the expression of MAGE-A, NY-ESO-1, CT7 (MAGE-C1), and GAGE7 (CT4.7), which have been well studied in a variety of other tumours, in a large series of these carcinomas. 5,[12][13][14][15][16][17][18] We then focused on the expression and clinicopathological impact of MAGE-A and NY-ESO-1 in adenoid cystic carcinomas (AdCCs), because: (i) AdCCs are among the most common carcinomas of the salivary gland; (ii) MAGE-A was frequently expressed in AdCC in the present study; and (iii) MAGE-A and NY-ESO-1 have been investigated in clinical trials of targeted therapy for other solid tumours. 5,[12][13][14][15]19…”

Section: Introductionmentioning

confidence: 99%