mRNA expression of MAGE-A3 gene in leukemia cells

Martı́nez, A. Pérez; Olarte, Irma; Mergold, M.A.; Gutiérrez, Mario; Rozen, Etta; Collazo, Juan; Amancio-Chassin, Octavio; Ordoñez, Rosa M.; Montesinos, Juan José; Mayani, Héctor; McCurdy, Deborah; Ostrosky‐Wegman, Patricia; Garrido-Guerrero, Efraín; Miranda, Enrique

doi:10.1016/j.leukres.2006.05.009

Cited by 31 publications

(26 citation statements)

References 17 publications

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“…86 Scheibenbogen et al 87 were the first to describe the natural existence of CD8 þ T-cell immunity against PR1 and WT1 126-134 in patients with AML, both at diagnosis and in complete remission. 87 These findings were corroborated by the later work of Rezvani et al, 73 who observed spontaneous T-cell responses to PR1 and WT1 [126][127][128][129][130][131][132][133][134] in two out of eight patients before immunization with a combined PR1/WT1 peptide vaccine. 73 In a separate study, the same group found that such CTL responses were not limited to the immunodominant WT1 [126][127][128][129][130][131][132][133][134] epitope, but could also be directed against other HLA-A*0201-restricted WT1-derived epitopes (WT1 [37][38][39][40][41][42][43][44][45] , WT1 [187][188][189][190][191][192][193][194][195] and WT1 [235][236][237][238][239][240][241][2...…”

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 57%

“…16 This peptide sequence also encompasses the HLA-DP5-restricted WT1 337-347 epitope 70 as well as the WT1 333-347 epitope, which can be recognized by CD4 þ regulatory T cells in the context of HLA-DR4. 71 Other WT1 helper epitopes with direct relevance to AML immunotherapy are WT1 427-445 and WT1 [122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140] . 69 The latter contains another immunogenic CD4 þ T-cell epitope, WT1 [124][125][126][127][128][129][130][131][132][133][134][135][136][137][138] , and the HLA-A*0201-restricted CD8 þ T-cell epitope, WT1 [126][127][128][129][130][131][132][133][134] , 16 and is thus capable of stimulating a combined CD8 þ /CD4 þ WT1-specific T-cell immune response.…”

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 99%

“…These studies, including WT1 peptide and WT1-targeted dendritic cell vaccine trials, have unequivocally established that CD8 þ T-cell immune responses specific to WT1 can be induced by active immunization in a substantial number of AML patients. 14 In those patients, multiple WT1 CTL epitopes have been recognized as immunogenic (including WT1 [37][38][39][40][41][42][43][44][45] , WT1 [126][127][128][129][130][131][132][133][134] , WT1 [187][188][189][190][191][192][193][194][195] and WT1 [235][236][237][238][239][240][241][242][243] ), demonstrating the excellent in vivo immunostimulatory potential of WT1 (Table 1). 14,72 This is further supported by the capacity to induce WT1-specific CD4 þ helper T-cell immunity in patients with AML through active immunization.…”

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 99%

“…74 The clinical relevance of PR1 is further supported by the observation of a significant disease-free survival advantage and a trend toward improved overall survival in patients with myeloid malignancies developing immunity to PR1 after peptide immunization. 94 In a clinical trial of combined PR1/WT1 [126][127][128][129][130][131][132][133][134] peptide vaccination, Rezvani et al 73 demonstrated that the induction of high-avidity PR1-and/or WT1-specific CTLs was critically required to achieve clinical response (reduction of WT1 transcript levels). 73 Schmitt et al 47 assessed the clinical effectiveness of RHAMM 165-173 peptide vaccination in a mixed cohort of patients with hematological malignancies, including three patients with AML.…”

Section: Criterion 5: Clinical Relevancementioning

confidence: 99%

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Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

2012

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The graft-versus-leukemia effect of allogeneic hematopoietic stem cell transplantation (HSCT) has shown that the immune system is capable of eradicating acute myeloid leukemia (AML). This knowledge, along with the identification of the target antigens against which antileukemia immune responses are directed, has provided a strong impetus for the development of antigen-targeted immunotherapy of AML. The success of any antigen-specific immunotherapeutic strategy depends critically on the choice of target antigen. Ideal molecules for immune targeting in AML are those that are: (1) leukemia-specific; (2) expressed in most leukemic blasts including leukemic stem cells; (3) important for the leukemic phenotype; (4) immunogenic; and (5) clinically effective. In this review, we provide a comprehensive overview on AML-related tumor antigens and assess their applicability for immunotherapy against the five criteria outlined above. In this way, we aim to facilitate the selection of appropriate target antigens, a task that has become increasingly challenging given the large number of antigens identified and the rapid pace at which new targets are being discovered. The information provided in this review is intended to guide the rational design of future antigen-specific immunotherapy trials, which will hopefully lead to new antileukemia therapies with more selectivity and higher efficacy.

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Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 57%

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 99%

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 99%

Section: Criterion 5: Clinical Relevancementioning

confidence: 99%

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Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

2012

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“…The overall absence of the majority of CT genes from AML samples is in line with earlier studies. Most CTA including MAGE-C1 [26], NY-ESO-1 [27][28][29], SSX-2 [27][28][29], and several members of the MAGE-A family of genes [29][30][31][32][33] were either completely absent from AML patient samples or evidenced only very low expression frequencies.…”

Section: Discussionmentioning

confidence: 99%

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

et al. 2011

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Cancer-testis antigens (CTA) represent attractive targets for tumor immunotherapy. However, a broad picture of CTA expression in acute myeloid leukemia (AML) is missing. CTA expression was analyzed in normal bone marrow (BM) as well as in AML cell lines before and after treatment with demethylating agents and/or histone acetylase inhibitors. Presence of selected CTA with a strictly tumor-restricted expression was then determined in samples of patients with AML before and after demethylating therapy. Screening AML cell lines for the expression of 20 CTA, we identified six genes (MAGE-A3, PRAME, ROPN1, SCP-1, SLLP1, and SPO11) with an AML-restricted expression. Analyzing the expression of these CTA in blast-containing samples from AML patients (N 5 64), we found all samples to be negative for MAGE-A3 and SPO11 while a minority of patients expressed ROPN1 (1.6%), SCP-1 (3.1%), or SLLP1 (9.4%). The only CTA expressed in substantial proportion of patients (53.1%) was PRAME. Following demethylating treatment with 5 0 -aza-2 0 -deoxycytidine, we observed an increased or de novo expression of CTA, in particular of SSX-2, in AML cell lines. In AML patients, we detected increased expression of PRAME and induction of SSX-2 after demethylating therapy with 5-azacytidine. With the exception of PRAME, CTA are mostly absent from AML blasts. However, demethylating treatment induces strong expression of CTA, particularly of SSX-2, in vitro and in vivo. Therefore, we propose that CTA-specific immunotherapy for AML should preferentially target PRAME and/or should be combined with the application of demethylating agents opening the perspective for alternative targets like CTA SSX-2. Am. J. Hematol. 86:918-922, 2011. V

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Effect of ionic content, solid content, degree of neutralization, and chain extension on aqueous polyurethane dispersions prepared by prepolymer method

Nanda¹,

Wicks²,

Madbouly³

et al. 2005

J of Applied Polymer Sci

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There are many variables in the preparation of aqueous polyurethane (PU) dispersions. Carboxylic acid content, solid content, degree of pre/postneutralization of the carboxylic acids, and chain extension all impact dispersion particle size, viscosity, pH, molecular weights, and glass transition temperature. This study evaluated the impact of these variables on a given PU dispersion formulation prepared from isophorone diisocyanate, an aliphatic polyester polyol, dimethylol propionic acid, and hexamethylene diamine with triethyl amine as the neutralizing base and N-methyl pyrrolidone as the cosolvent. Changes in carboxylic acid content, degree of preneutralization, and chain extension were found to have the expected impacts on dispersions properties. Increased ionic content in the dispersion step led to lower particle size and higher viscosity, increased chain extension with its concurrent increase in molecular improved subsequent film properties. Surprising results were obtained by varying the amount of postneutralization and from increased solids content at the time of dispersion. Unexpectedly, both of these variations led to much higher dispersion viscosities and particle size in solution. To have these changes take place, it is theorized that there is a major change in solution morphology caused by these modifications.

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mRNA expression of MAGE-A3 gene in leukemia cells

Cited by 31 publications

References 17 publications

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

Effect of ionic content, solid content, degree of neutralization, and chain extension on aqueous polyurethane dispersions prepared by prepolymer method

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