Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) Patients

Greiner, Jochen; Brown, Elliott C.; Bullinger, Lars; Hills, Robert Kerrin; Morris, Vanessa; Döhner, Hartmut; Mills, Ken I.; Guinn, Barbara

doi:10.3390/ijms221910482

Cited by 6 publications

(15 citation statements)

References 59 publications

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“…Dos Santos et al [23] Xu et al [24] Darwish et al [25] Xiao et al [26] Wang et al [27] Xu et al [28] Haubner et al [29] Abdellateif et al [30] Vollmer et al [31] Zhu et al [32] Lin et al [33] Tian et al [34] Xu et al [35] Basharat et al [36] Alanazi et al [37] Greiner et al [38] Shin et al [39] Dou et al [40] Padró et al [41] Assi et al [42] Venditti et al [43] Xu et al [24] Table 3. Risk of bias and quality assurance using the QUADAS-2 system of article assessment.…”

Section: Patient Selection Interventionmentioning

confidence: 99%

A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis

Morris

Ghazi

Fletcher

et al. 2023

IJMS

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Acute myeloid leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral blood. Although AML can occur at any age, the incidence peaks at age 65. The pathobiology of AML also varies with age with associated differences in incidence, as well as the frequency of cytogenetic change and somatic mutations. In addition, 5-year survival rates in paediatrics are 60–75% but fall to 5–15% in older AML patients. This systematic review aimed to determine whether the altered genes in AML affect the same molecular pathways, indifferent of patient age, and, therefore, whether patients could benefit from the repurposing drugs or the use of the same immunotherapeutic strategies across age boundaries to prevent relapse. Using a PICO framework and PRISMA-P checklist, relevant publications were identified using five literature databases and assessed against an inclusion criteria, leaving 36 articles, and 71 targets for therapy, for further analysis. QUADAS-2 was used to determine the risk of bias and perform a quality control step. We then priority-ranked the list of cancer antigens based on predefined and pre-weighted objective criteria as part of an analytical hierarchy process used for dealing with complex decisions. This organized the antigens according to their potential to act as targets for the immunotherapy of AML, a treatment that offers an opportunity to remove residual leukaemia cells at first remission and improve survival rates. It was found that 80% of the top 20 antigens identified in paediatric AML were also within the 20 highest scoring immunotherapy targets in adult AML. To analyse the relationships between the targets and their link to different molecular pathways, PANTHER and STRING analyses were performed on the 20 highest scoring immunotherapy targets for both adult and paediatric AML. There were many similarities in the PANTHER and STRING results, including the most prominent pathways being angiogenesis and inflammation mediated by chemokine and cytokine signalling pathways. The coincidence of targets suggests that the repurposing of immunotherapy drugs across age boundaries could benefit AML patients, especially when used in combination with conventional therapies. However, due to cost implications, we would recommend that efforts are focused on ways to target the highest scoring antigens, such as WT1, NRAS, IDH1 and TP53, although in the future other candidates may prove successful.

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Section: Patient Selection Interventionmentioning

confidence: 99%

A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis

Morris

Ghazi

Fletcher

et al. 2023

IJMS

Self Cite

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“…Survivin is coded by the baculoviral IAP repeat-containing 5 (BIRC5) gene. It has been found to be involved in several central pathways that control cell viability and proliferation [ 30 , 31 ].…”

Section: Immunotherapies Targeting Immunogenic Leukemia-associated An...mentioning

confidence: 99%

Increasing Role of Targeted Immunotherapies in the Treatment of AML

Greiner

Götz

Wais

2022

IJMS

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Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The standard of care in medically and physically fit patients is intensive induction therapy. The majority of these intensively treated patients achieve a complete remission. However, a high number of these patients will experience relapse. In patients older than 60 years, the results are even worse. Therefore, new therapeutic approaches are desperately needed. One promising approach in high-risk leukemia to prevent relapse is the induction of the immune system simultaneously or after reduction of the initial tumor burden. Different immunotherapeutic approaches such as allogenic stem cell transplantation or donor lymphocyte infusions are already standard therapies, but other options for AML treatment are in the pipeline. Moreover, the therapeutic landscape in AML is rapidly changing, and in the last years, a number of immunogenic targets structures eligible for specific therapy, risk assessment or evaluation of disease course were determined. For example, leukemia-associated antigens (LAA) showed to be critical as biomarkers of disease state and survival, as well as markers of minimal residual disease (MRD). Yet many mechanisms and properties are still insufficiently understood, which also represents a great potential for this form of therapy. Therefore, targeted therapy as immunotherapy could turn into an efficient tool to clear residual disease, improve the outcome of AML patients and reduce the relapse risk. In this review, established but also emerging immunotherapeutic approaches for AML patients will be discussed.

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“…So, there is no current clinical trials using RHAMM CAR-T/NK Colonic Expressed in AML primary cells, possibly in LSCs Yes Possible Yes [ 73 ] Survivin Intracellular peptides Anti-apoptotic proteins (associated with embryogenesis) Used in vaccine test. It is temporarily unable to attach antigen to CAR, so there are no current clinical trials using Survivin CAR-T/NK Endothelial cells Expressed on AML primary cells, LSC Yes Yes Yes [ 74 , 75 ] hTERT Intracellular peptides Telomerase complex subunit Used in vaccine test. It is temporarily unable to attach antigen to CAR, so there are no current clinical trials using hTERT CAR-T/NK Keratinocytes, testis, endothelial cells, placenta Expressed in AML primary cells, possibly in LSC Yes(low) Possible Yes [ 76 – 78 ] CD4 T lymphocyte membrane glycoprotein Interaction with major histocompatibility complex class II antigens No current clinical trials using CD4 CAR-T/NK are recruiting.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers as targets for CAR-T/NK cell therapy in AML

Shao

Xin

et al. 2023

Biomark Res

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The most common kind of acute leukemia in adults is acute myeloid leukemia (AML), which is often treated with induction chemotherapy regimens followed by consolidation or allogeneic hematopoietic stem cell transplantation (HSCT). However, some patients continue to develop relapsed or refractory AML (R/R-AML). Small molecular targeted drugs require long-time administration. Not all the patients hold molecular targets. Novel medicines are therefore needed to enhance treatment outcomes. T cells and natural killer (NK) cells engineered with chimeric antigen receptors (CARs) that target antigens associated with AML have recently been produced and are currently being tested in both pre-clinical and clinical settings. This review provides an overview of CAR-T/NK treatments for AML.

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Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) Patients

Cited by 6 publications

References 59 publications

A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis

A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis

Increasing Role of Targeted Immunotherapies in the Treatment of AML

Biomarkers as targets for CAR-T/NK cell therapy in AML

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