Antibody-based immunotherapy of leukemia requires the targeting of specific antigens on the surface of blasts. The Fc gamma receptor (CD64) has been investigated in detail, and CD64-targeting immunotherapy has shown promising efficacy in the targeted ablation of acute myeloid leukemia (AML), acute myelomonocytic leukemia (AMML) and chronic myeloid leukemia cells (CML). Here we investigate for the first time the potential of FcαRI (CD89) as a new target antigen expressed by different myeloid leukemic cell populations. For specific targeting and killing, we generated a recombinant fusion protein comprising an anti-human CD89 single-chain Fragment variable and the well-characterized truncated version of the potent Pseudomonas aeruginosa exotoxin A (ETA'). Our novel therapeutic approach achieved in vitro EC50 values in range 0.2-3 nM depending on the applied stimuli, that is, interferon gamma or tumor necrosis factor alpha. We also observed a dose-dependent apoptosis-mediated cytotoxicity, which resulted in the elimination of up to 90% of the target cells within 72 hr. These findings were also confirmed ex vivo using leukemic primary cells from peripheral blood samples of three previously untreated patients. We conclude that CD89-specific targeting of leukemia cell lines can be achieved in vitro and that the efficient elimination of leukemic primary cells supports the potential of CD89-ETA' as a potent, novel immunotherapeutic agent.
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http://dx.doi.org/10.1002/ijc.29628 | DOI Listing |
Bone Marrow Transplant
January 2025
Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Wake Forest University School of Medicine, Charlotte, NC, USA.
Blood Cancer J
January 2025
Hospital de la Santa Creu i Sant Pau. Institut d'investigació Biomèdica Sant Pau (IIB SANT PAU) Department of Medicine, Universitat Autonoma of Barcelona, Barcelona, Spain.
Given the heterogeneity of acute myeloid leukemia patients, it is necessary to identify patients considered fit for intensive therapy but who will perform poorly, and in whom alternative approaches deserve investigation. We analyzed 1034 fit adults ≤70 years intensively treated between 2012 and 2022 in the CETLAM group. Young adults ( ≤ 60 years) presented higher remission rates and improved survival than older adults above that age (CR 79% vs.
View Article and Find Full Text PDFClin Lymphoma Myeloma Leuk
December 2024
Section of Benign Hematology, Department of Internal Medicine, MD Anderson Cancer Center, Houston, TX. Electronic address:
Background: 'Standard of care' therapies for adult acute myeloid leukemia (AML) have yielded 5-year overall survival (OS) rates of 30%-45 %. Risk stratification and novel targeted therapies have improved 5-year OS rates to >75 % for certain groups in specialized centers.
Patients And Methods: This is a retrospective cohort analysis of outcomes in patients ≥18 years with newly diagnosed AML treated between 2005 and 2019 in the Harris Health County, Safety-Net Hospital System in Houston, TX.
Cancer Genet
January 2025
PhD of Hematology, Assistant Professor, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:
J Cell Mol Med
January 2025
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells offer an opportunity for a standardized, off-the-shelf treatment with the potential to treat a wider population of acute myeloid leukaemia (AML) patients than the current standard of care. FT538 iPSC-NKs express a high-affinity, noncleavable CD16 to maximize antibody dependent cellular cytotoxicity, a CD38 knockout to improve metabolic fitness, and an IL-15/IL-15 receptor fusion preventing the need for cytokine administration, the main source of adverse effects in NK cell-based therapies. Here, we sought to evaluate the potential of FT538 iPSC-NKs as a therapy for AML through their effect on AML cell lines and primary AML cells.
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