Post-transplant immunotherapy with WT1-specific CTLs for high-risk acute myelogenous leukemia: a prospective clinical phase I/II trial

Kim, Hee-Je; Sohn, Honglae; Hong, Jung-A; Lee, Hyun-Joo; Sohn, Dae-Hee; Shin, Chang-Ae; Cho, Hyun-Il; Min, Woo-Sung; Kim, Tai‐Gyu

doi:10.1038/s41409-018-0383-2

Cited by 12 publications

(10 citation statements)

References 14 publications

(14 reference statements)

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“…Moreover, the expression increased during myelofibrotic transformation and high WT1 transcript levels could be linked to splenomegaly and thrombocytopenia and overexpression of WT1 was hypothesized to play an important role in the leukemic transformation of MPN [ 201 , 202 ]. Comparable with the results reported about WT1 expression in MPN, its expression is also higher in leukemia cells and LSCs compared to normal healthy hematopoietic cells and is a possible prognostic factor to predict clinical outcome and to detect MRD [ 203 , 204 , 205 , 206 ]. WT1 is a possible antigen to specifically target in leukemia patients as it was demonstrated that WT1-reactive cytotoxic T-cells mediate a strong anti-tumor immune response in post-transplant patients [ 207 ].…”

Section: Wt1-specific T-cellssupporting

confidence: 62%

“…The expansion of these cells was correlated with an increased GvL reaction in patients with ALL [ 208 ]. Further strategies, including the transfer of WT1-specific T-cells or autologous vaccination of AML patients with the WT1 peptide, did increase anti-leukemia immune responses in relapsed or high-risk leukemia patients [ 203 , 207 , 209 ]. These findings drew attention to the transfer of WT1-specific cytotoxic T-cells into AML patients.…”

Section: Wt1-specific T-cellsmentioning

confidence: 99%

“…The comparison group had only 54% relapse-free survival ( Identifier: NCT01640301) [ 206 ]. In a second study, Kim et al demonstrated that in vitro generation of WT1-specific cytotoxic T lymphocytes and subsequent transfer is a feasible therapeutic approach for the treatment of AML patients being at high risk of relapse after allo-HSCT [ 203 ]. Summarizing these studies, the transfer of cytotoxic T-cells specifically targeting the WT1 antigen together with allogeneic or autologous T-cells in high-risk AML patients could be a promising strategy to enhance a strong and specific anti-leukemia immune reaction and to prevent AML recurrence in these patients [ 203 , 206 ].…”

Section: Wt1-specific T-cellsmentioning

confidence: 99%

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Immunotherapy in Myeloproliferative Diseases

Braun

Zeiser

2020

Cells

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Myeloproliferative diseases, including myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS), are driven by genetic abnormalities and increased inflammatory signaling and are at high risk to transform into acute myeloid leukemia (AML). Myeloid-derived suppressor cells were reported to enhance leukemia immune escape by suppressing an effective anti-tumor immune response. MPNs are a potentially immunogenic disease as shown by their response to interferon-α treatment and allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Novel immunotherapeutic approaches such as immune checkpoint inhibition, tumor vaccination, or cellular therapies using target-specific lymphocytes have so far not shown strong therapeutic efficacy. Potential reasons could be the pro-inflammatory and immunosuppressive microenvironment in the bone marrow of patients with MPN, driving tumor immune escape. In this review, we discuss the biology of MPNs with respect to the pro-inflammatory milieu in the bone marrow (BM) and potential immunotherapeutic approaches.

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Section: Wt1-specific T-cellssupporting

confidence: 62%

Section: Wt1-specific T-cellsmentioning

confidence: 99%

Section: Wt1-specific T-cellsmentioning

confidence: 99%

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Immunotherapy in Myeloproliferative Diseases

Braun

Zeiser

2020

Cells

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“…Numerous clinical studies were carried out implementing peptide vaccination strategies for AML patients in remission after an initial chemotherapy and demonstrated that they are able to induce T-cell responses and are well tolerated with only minor side effects [79,118,119,120]. Furthermore, DC vaccination and adoptive transfer of WT1-specific cytotoxic T cells showed to be auspicious therapeutic options in combination with allogeneic stem cell transplantation in AML patients [121,122].…”

Section: Hla-dependent Antigensmentioning

confidence: 99%

Antigen Targets for the Development of Immunotherapies in Leukemia

Bauer

Nelde

Bilich

et al. 2019

IJMS

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Immunotherapeutic approaches, including allogeneic stem cell transplantation and donor lymphocyte infusion, have significantly improved the prognosis of leukemia patients. Further efforts are now focusing on the development of immunotherapies that are able to target leukemic cells more specifically, comprising monoclonal antibodies, chimeric antigen receptor (CAR) T cells, and dendritic cell- or peptide-based vaccination strategies. One main prerequisite for such antigen-specific approaches is the selection of suitable target structures on leukemic cells. In general, the targets for anti-cancer immunotherapies can be divided into two groups: (1) T-cell epitopes relying on the presentation of peptides via human leukocyte antigen (HLA) molecules and (2) surface structures, which are HLA-independently expressed on cancer cells. This review discusses the most promising tumor antigens as well as the underlying discovery and selection strategies for the development of anti-leukemia immunotherapies.

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“…The group recently published a larger series of 8 patients with relapsed or refractory (r/r) AML who received HSCT followed by infusions of donor-derived WT1-specific T cells. While 3 patients relapsed within 1 year post-infusion, five remain in long-term CR (>8 years) 9 .…”

Section: B211 Donor-derived Productsmentioning

confidence: 99%

Adoptive Cell Therapy for Acute Myeloid Leukemia and T-Cell Acute Lymphoblastic Leukemia

2019

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Refractory and relapsed acute myeloid leukemia (AML) and T-lineage leukemia (T-ALL) have poor prognosis and limited therapeutic options. Adoptive cellular immunotherapies are emerging as an effective treatment for patients with chemotherapy refractory hematological malignancies. Indeed the use of unselected donor lymphocyte infusions (DLIs) have demonstrated successes in treating patients with AML and TALL post-allogeneic The development of ex vivo manipulation techniques such as genetic modification or selection and expansion of individual cellular components has permitted the clinical translation of a wide range of promising cellular therapies for AML and TALL. Here, we will review clinical studies to date using adoptive cell therapy approaches and outline the major challenges limiting the development of safe and effective cell therapies for both types of acute leukemia.

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Post-transplant immunotherapy with WT1-specific CTLs for high-risk acute myelogenous leukemia: a prospective clinical phase I/II trial

Cited by 12 publications

References 14 publications

Immunotherapy in Myeloproliferative Diseases

Immunotherapy in Myeloproliferative Diseases

Antigen Targets for the Development of Immunotherapies in Leukemia

Adoptive Cell Therapy for Acute Myeloid Leukemia and T-Cell Acute Lymphoblastic Leukemia

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