A novel MHC-associated Proteinase 3 peptide isolated from primary chronic myeloid leukaemia cells further supports the significance of this antigen for the immunotherapy of myeloid leukaemias

Knights, Ashley; Weinzierl, Andreas O.; Flad, Thomas; Guinn, Barbara; Mueller, L.; Mufti, Ghulam J.; Stevanović, Stefan; Pawelec, Graham

doi:10.1038/sj.leu.2404234

Cited by 18 publications

(10 citation statements)

References 19 publications

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“…Examples of these antigens are human telomerase reverse transcriptase [25], survivin [26,27], proteinase-3 [28,29], Wilms tumor gene-encoded transcription factor-1 (WT1) [30,31], mucin-1 [32], and preferentially expressed antigen of melanoma (PRAME) [33], which can be found only at very low levels in healthy tissues, such as the adrenal glands, ovaries, and endometrium. Shared TAA have been considered as potential targets for cancer immunotherapy.…”

Section: Classification Of Tumor Antigensmentioning

confidence: 99%

“…Reports of PRAME antigen expression range from 47% to 70% of AML patients [37,38]. Proteinase-3 is also overexpressed in AML and CML [28,39,40] and WT1 is overtly present in several different types of leukemia [41]. In fact, WT1 ranked in the top 20 antigens with suggestive high therapeutic functionality according to the National Cancer Institute report on the prioritization of cancer antigens for acceleration of translational research [42].…”

Section: Classification Of Tumor Antigensmentioning

confidence: 99%

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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%

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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“…Immunotherapy with T cells using unmanipulated donor lymphocyte infusion (DLI) for the treatment of leukaemia recurrence in Haematological Stem Cells Transplantation (HSCT) recipients has shown some positive results in AML, but the use of DLI carries a significant risk of inducing Graft versus Host Disease (GvHD) [17]. The identification of leukaemia-associated antigens eliciting T-cell responses in vitro , has been successful for AML [18]. However, the generation of leukaemia-specific cytotoxic T cells against AML-associated antigens has been hampered by several factors: the poor immunogenicity of blasts lacking costimulatory molecules and the low frequency of T-cell precursors in antigen-naïve marrow donors or in patients anergized by their own leukaemia.…”

Section: Clinical Application In Haematologymentioning

confidence: 99%

New advances in leukaemia immunotherapy by the use of Chimeric Artificial Antigen Receptors (CARs): state of the art and perspectives for the near future

et al. 2011

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Leukaemia immunotherapy represents a fascinating and promising field of translational research, particularly as an integrative approach of bone marrow transplantation. Adoptive immunotherapy by the use of donor-derived expanded leukaemia-specific T cells has showed some kind of clinical response, but the major advance is nowadays represented by gene manipulation of donor immune cells, so that they acquire strict specificity towards the tumour target and potent lytic activity, followed by significant proliferation, increased survival and possibly anti-tumour memory state. This is achieved by gene insertion of Chimeric T-cell Antigen Receptors (CARs), which are artificial molecules containing antibody-derived fragments (to bind the specific target), joined with potent signalling T-Cell Receptor (TCR)-derived domains that activate the manipulated cells. This review will discuss the main application of this approach particularly focusing on the paediatric setting, raising advantages and disadvantages and discussing relevant perspectives of use in the nearest future.

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“…Matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) MS and its derivative surface enhanced laser desorption and ionization (SELDI)-TOF MS are enabling technologies which have increased the sensitivity and throughput for the detection of novel leukemia antigens. MALDI-TOF MS has previously been applied to chronic myeloid leukemia (Knights et al 2006) to identify processed and presented epitopes eluted from MHC which led to the identification of a novel peptide from PRTN3, which was detected among the more abundant MHC-ligands. It can only be a matter of time before the same technology is used to identify epitopes in LAAs that are processed and presented on primary AML samples.…”

Section: Assays For Identifying New Biomarkers/laasmentioning

confidence: 99%

Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

et al. 2007

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Leukemia associated antigens (LAAs) are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL) cloning, serological analysis of recombinant cDNA expression libraries (SEREX) and mass spectrometry (MS). In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs), serial analysis of gene expression (SAGE) and 2-dimensional gel electrophoresis (2-DE) have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML). It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel) and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.

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A novel MHC-associated Proteinase 3 peptide isolated from primary chronic myeloid leukaemia cells further supports the significance of this antigen for the immunotherapy of myeloid leukaemias

Cited by 18 publications

References 19 publications

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

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

New advances in leukaemia immunotherapy by the use of Chimeric Artificial Antigen Receptors (CARs): state of the art and perspectives for the near future

Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

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