Complete molecular response in CML after p210 BCR–ABL1-derived peptide vaccination

Bocchia, Monica; Defina, Marzia; Aprile, Lara; Ippoliti, Micaela; Crupi, Rosaria; Rondoni, Michela; Gozzetti, Alessandro; Lauria, Francesco

doi:10.1038/nrclinonc.2010.141

Cited by 27 publications

(18 citation statements)

References 14 publications

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“…Most immune reactivities found after DLI against any of these antigens are weak. Moreover, immune reactivity against autologous antigens is frequently suppressed by mechanisms of tolerance mediated by, e.g., regulatory T-cells (Tregs) or inhibitory cytokines (104). Peptides presented by foreign HLA antigens can be immunogenic by different configurations (105).…”

Section: Improvement Of the Responsementioning

confidence: 99%

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

et al. 2017

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The success of hematopoietic stem cell transplantation (HSCT) lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL), caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter.

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Section: Improvement Of the Responsementioning

confidence: 99%

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

et al. 2017

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“…116 Larger observational studies of junctional peptide vaccination of chronic phase CML patients on imatinib (www.clinicaltrials.gov identifier NCT00466726) have demonstrated T-cell responses and reductions in BCR-ABL1 transcripts in vaccine recipients, 117–119 whereas sustained CMRs in the absence of TKI therapy have been reported in a few vaccinated patients. 120,121 …”

Section: Immunological Approaches To CML Stem Cell Eradicationmentioning

confidence: 99%

Alternative approaches to eradicating the malignant clone in chronic myeloid leukemia: tyrosine-kinase inhibitor combinations and beyond

Ahmed

Etten

2013

Hematology

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In patients with chronic myeloid leukemia (CML) in chronic phase who have achieved complete molecular remission on imatinib therapy, clinical trials from France and Australia have demonstrated that the majority experience prompt molecular relapse of their leukemia upon discontinuation of the drug, showing that long-term monotherapy with tyrosine kinase inhibitors is not curative in the majority of patients with CML. This has focused attention on strategies to eradicate residual disease in CML that is presumed to arise from malignant Ph+ stem cells, which should result in permanent cure and long-term leukemia-free survival. Here, we review the evidence that targeting CML stem cells will be of clinical benefit and discuss pharmacological and immunological approaches to accomplish this goal. Where possible, we link preclinical studies of CML stem cell biology to emerging results from clinical trials of agents that may target these cells.

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“…The role of the patient's own immune system in recognizing BCR-ABL-expressing cells, and whether this can be boosted for beneficial effect, is currently under investigation in vaccination studies, although no convincing results have been reported. 7,8 Similarly, it is not known whether immune recognition by the patient's immune system is playing a part in maintaining remission of nonrelapsing patients in whom TKI treatment is discontinued.…”

Section: Introductionmentioning

confidence: 99%

CML cells actively evade host immune surveillance through cytokine-mediated downregulation of MHC-II expression

Tarafdar

Hopcroft

Gallipoli

et al. 2017

Blood

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Key Points• MHC-II and its master regulator CIITA are downregulated in CML stem/ progenitor cells in a BCR-ABL kinase-independent manner. • JAK1/2 inhibition increased MHC-II expression, suggesting elevation of CML immunogenicity may provide a way to reduce CML persistence.Targeting the fusion oncoprotein BCR-ABL with tyrosine kinase inhibitors has significantly affected chronic myeloid leukemia (CML) treatment, transforming the life expectancy of patients; however the risk for relapse remains, due to persistence of leukemic stem cells (LSCs). Therefore it is imperative to explore the mechanisms that result in LSC survival and develop new therapeutic approaches. We now show that major histocompatibility complex (MHC)-II and its master regulator class II transactivator (CIITA) are downregulated in CML compared with non-CML stem/progenitor cells in a BCR-ABL kinase-independent manner. Interferon g (IFN-g) stimulation resulted in an upregulation of CIITA and MHC-II in CML stem/progenitor cells; however, the extent of IFN-g-induced MHC-II upregulation was significantly lower than when compared with non-CML CD34 1 cells. Interestingly, the expression levels of CIITA and MHC-II significantly increased when CML stem/progenitor cells were treated with the JAK1/2 inhibitor ruxolitinib (RUX). Moreover, mixed lymphocyte reactions revealed that exposure of CD34 1 CML cells to IFN-g or RUX significantly enhanced proliferation of the responder CD4 1 CD69 1 T cells. Taken together, these data suggest that cytokine-driven JAKmediated signals, provided by CML cells and/or the microenvironment, antagonize MHC-II expression, highlighting the potential for developing novel immunomodulatory-based therapies to enable host-mediated immunity to assist in the detection and eradication of CML stem/progenitor cells. (Blood. 2017;129(2):199-208)

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Complete molecular response in CML after p210 BCR–ABL1-derived peptide vaccination

Cited by 27 publications

References 14 publications

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

Alternative approaches to eradicating the malignant clone in chronic myeloid leukemia: tyrosine-kinase inhibitor combinations and beyond

CML cells actively evade host immune surveillance through cytokine-mediated downregulation of MHC-II expression

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