CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia

Scheibenbogen, Carmen; Letsch, Anne; Thiel, Eckhard; Schmittel, Alexander; Mailänder, Volker; Baerwolf, Steffi; Nagorsen, Dirk; Keilholz, Ulrich

doi:10.1182/blood-2002-01-0163

Cited by 239 publications

(191 citation statements)

References 31 publications

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“…Greiner et al 86 demonstrated that such serological responses could be detected in over one-third of AML patients. 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.…”

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 99%

“…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: 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: 99%

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 99%

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

2012

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“…16 Stimulation was considered to be positive if the difference between the peptide-specific stimulation and the negative control exceeded 0.1% of all CD3 þ /CD8 þ T cells 19 with at least 250 000 living cells to be enumerated. To analyze the generated CTL lines, IFN-g assay was performed either with peptide-loaded autologous DC or with primary tumor cells as stimulators at the ratio of 5:1 (CTL: DC/tumor cells).…”

Section: Preparation Of Pbmcs and Generation Of Dcsmentioning

confidence: 99%

CD8+ T-cell responses to tumor-associated antigens correlate with superior relapse-free survival after allo-SCT

Kapp

Stevanović

Fick

et al. 2009

Bone Marrow Transplant

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The GVL effect following allo-SCT is one of the most prominent examples showing the ability of the immune system to eliminate malignant hematological diseases. Tumor-associated Ags (TAA), for instance WT1 and proteinase-3, have been proposed as targets for T cells to establish a GVL effect. Here, we examined an additional TAA (MUC1) as a possible T-cell target of GVL-related immune responses. We have defined new peptide epitopes from the MUC1 Ag to broaden patients' screening and to expand the repertoire of immunologic monitoring as well as for therapeutic approaches in the future. Twenty-eight patients after allo-SCT have been screened for T-cell responses toward TAA (proteinase-3, WT1, MUC1). We could detect a significant relationship between relapse and the absence of a TAA-specific T-cell response, whereby only 2/13 (15%) patients with TAA-specific CTL relapsed, in contrast to 9/15 (60%) patients without TAA-specific CTL responses (Po0.05). In conclusion, CD8 þ T-cell responses directed to TAA might contribute to the GVL effect. These observations highlight both the importance and the potential of immunotherapeutic approaches after allo-SCT.

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“…Furthermore, there is growing evidence for a specific T-cell response against AML-associated antigens, such as adipophillin, survivin, mucin-1, proteinase-1, Wilms' tumour-1 and others. [11][12][13][14] In this study, we aimed to determine whether alterations in APM components are also a possible immune escape mechanism used by AML blasts to evade specific recognition and elimination by the immune system. We studied the APM at different levels of protein processing and assembly of the MHCpeptide complex.…”

Section: Introductionmentioning

confidence: 99%

In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray

et al. 2009

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CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia

Abstract: Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in vitro and in murine models. We performed this study to investigate whether WT1-and proteinase 3-specific

Cited by 239 publications

References 31 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

CD8+ T-cell responses to tumor-associated antigens correlate with superior relapse-free survival after allo-SCT

In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray

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