Cellular immunotherapy for acute myeloid leukemia: How specific should it be?

Lee, Jong Bok; Chen, Branson; Vasic, Daniel; Law, Arjun; Zhang, Li

doi:10.1016/j.blre.2019.02.001

Cited by 22 publications

(28 citation statements)

References 132 publications

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“…In contrast to chemotherapy and new FDA-approved targeting agents, cellular CAR-T cell therapy and cytotoxic T lymphocytes can minimize systemic cytotoxicity and morbidity while generating maximal anti-tumor activity (22). However, in this study, we did observe low anti-CLL1 CAR T-cells expansion during the CAR T-cell therapy.…”

Section: Discussioncontrasting

confidence: 78%

“…In addition, the overall prognosis for patients with this treatment has remained stagnant in the last two decades (18,19). With the advent of next generation sequencing (NGS), more and more prognostically cytogenetic and molecular markers have been incorporated into AML risk classification and therapy (20)(21)(22). For example, tyrosine kinase inhibitors (FLT3-ITD inhibitor), IDH1 inhibitor ivosidenib, IDH2 inhibitor enasidenib, and BCL2 inhibitor venetoclax, monoclonal antibody-based therapy (anti-CD33 therapy); cellular therapy (CAR-T and TCR-engineered T-cell, and NK cell therapies), and novel regimens (decitabine and pracinostat) have been successfully developed (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, our prolonged survival observation in this patient with sAML showed that anti-CLL1 CAR-T might be of great potential in AML treatment. Interestingly, Liu F et al has reported the efficacy of combination CLL1-CD33 CAR-T cells in a 6-year-old girl with sAML transformed from prior faconi anemia and juvenile myelomonocytic leukemia (22). Given that B-cell aplasia is an indicator of CD19 CAR T-cell therapy, frequencies of CLL1 expressing mononuclear cells might be used as an indicator in a similar way, to monitor the efficacy of CAR T-cells.…”

Section: Discussionmentioning

confidence: 99%

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Successful Anti-CLL1 CAR T-Cell Therapy in Secondary Acute Myeloid Leukemia

et al. 2020

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Secondary acute myeloid leukemia (sAML) is a high-risk AML evolving from heterogenous prior hematological disorders. Compared to de novo AML, sAML has even worse responses to current therapy and thus is associated with lower remission rates, inferior overall survival (OS) and higher relapse rates. Many efforts have been devoted to improving the overall but with limited success, and novel strategy is thus highly needed. Recent research has identified that CLL1 is highly expressed on AML leukemia stem cells and blasts cells but not on normal hematopoietic stem cells. In this case report, we treated a secondary AML patient with anti-CLL1 CART therapy and achieved morphological, immunophenotypic and molecular complete remission for over 10 months. Although only one successful case is presented here, the anti-CLL1 CAR T-cells should be considered as another treatment option for secondary AML in the future.

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Successful Anti-CLL1 CAR T-Cell Therapy in Secondary Acute Myeloid Leukemia

et al. 2020

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“…Another adoptive T-cells transfer therapy that could be proposed is generated T-cells with a transgenic TCR specific to one antigen. A few tumor-specific proteins that act as leukemia-specific antigens (Tumor Specific Antigens, TSA), such as RUNX1-RUNX1T1, FLT3, and NPM1, have been described as being associated with AML (229), resulting from mutations (mutated TSA) or aberrant expression (aberrantly expressed TSA) from noncoding regions (230). C-terminal CLAVEEVSLRK sequence of NPM1c (DNPM1) binds and presents as HLA-A*02:01 (231).…”

Section: Transgenic T-cell Receptor (Tcr) T-cells Leading Competitorsmentioning

confidence: 99%

Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics

et al. 2020

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Recent studies have provided several insights into acute myeloid leukemia. Studies based on molecular biology have identified eight functional mutations involved in leukemogenesis, including driver and passenger mutations. Insight into Leukemia stem cells (LSCs) and assessment of cell surface markers have enabled characterization of LSCs from hematopoietic stem and progenitor cells. Clonal evolution has been described as having an effect similar to that of microenvironment alterations. Such biological findings have enabled the development of new targeted drugs, including drug inhibitors and monoclonal antibodies with blockage functions. Some recently approved targeted drugs have resulted in new therapeutic strategies that enhance standard intensive chemotherapy regimens as well as supportive care regimens. Besides the progress made in adoptive immunotherapy, since allogenic hematopoietic stem cell transplantation enabled the development of new T-cell transfer therapies, such as chimeric antigen receptor T-cell and transgenic TCR T-cell engineering, new promising strategies that are investigated.

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“…Cancer immunotherapy has shown promising potential in the treatment of hematopoietic and solid tumors in recent years, achieving long-lasting complete responses and improving the overall survival in a fraction of patients with refractory or metastatic cancers. 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 In the context of cancer immunotherapy, immune checkpoint inhibitors have achieved unprecedented success both in preclinical models and in clinical practice, with increasing approved indications and an increased response rate. However, patients who benefited from checkpoint inhibitors are still limited.…”

Section: Introductionmentioning

confidence: 99%

Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast Cancer

Zhang

Zhu

et al. 2020

Molecular Therapy - Oncolytics

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Increasing evidence demonstrates that microorganisms and their products can modulate host responses to cancer therapies and contribute to tumor shrinkage via various mechanisms, including intracellular signaling pathways modulation and immunomodulation. Detoxified pneumolysin derivative ΔA146Ply is a pneumolysin mutant lacking hemolytic activity. To determine the antitumor activity of ΔA146Ply, the combination of ΔA146Ply and berbamine, a well-established antitumor agent, was used for breast cancer therapy, especially for triple-negative breast cancer. The efficacy of the combination therapy was evaluated in vitro using four breast cancer cell lines and in vivo using a synergistic mouse tumor model. We demonstrated that in vitro , the combination therapy significantly inhibited cancer cell proliferation, promoted cancer cell apoptosis, caused cancer cell-cycle arrest, and suppressed cancer cell migration and invasion. In vivo , the combination therapy significantly suppressed tumor growth and prolonged the median survival time of tumor-bearing mice partially through inhibiting tumor cell proliferation, promoting tumor cell apoptosis, and activating systemic antitumor immune responses. The safety analysis demonstrated that the combination therapy showed no obvious liver and kidney toxicity to tumor-bearing mice. Our study provides a new treatment option for breast cancer and lays the experimental basis for the development of ΔA146Ply as an antitumor agent.

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Cellular immunotherapy for acute myeloid leukemia: How specific should it be?

Cited by 22 publications

References 132 publications

Successful Anti-CLL1 CAR T-Cell Therapy in Secondary Acute Myeloid Leukemia

Successful Anti-CLL1 CAR T-Cell Therapy in Secondary Acute Myeloid Leukemia

Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics

Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast Cancer

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