- |||||||||| Cd33-targeting sirna conjugates for treatment of alzheimer (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12421;
Subsequent studies will investigate therapeutic efficacy in the 5xFAD disease mouse model by assessing A? plaque density, neuroinflammation, and cognitive function.
- |||||||||| Journal: Targeting Inhibitory Siglec-3 to Suppress IgE-Mediated Human Basophil Degranulation. (Pubmed Central) - Aug 7, 2024
Pretreating human basophils with anti-IgE-CD33L significantly suppressed basophil degranulation through the IgE-Fc?RI complex. The ability to abrogate IgE-mediated basophil degranulation is of particular interest, as treatment with anti-IgE-CD33L before antigen exposure could have broad implications for the treatment of food, drug, and environmental allergies.
- |||||||||| CD33 competitive inhibitor peptide IMAD-001 modulates innate immunity in Alzheimer's disease (Exhibit (Pennsylvania Convention Center); In-Person) - Jun 19, 2024 - Abstract #AAIC2024AAIC_2532;
IMAD-001 inhibition of CD33 resolved A? induced suppressed microglial immune signaling and increased microglial phagocytosis and response to their environment in vitro and in vivo, without inducing inappropriate activation, suggesting its potential for therapeutic use in AD .
- |||||||||| Journal: Alzheimer's Disease Genetics: A Dampened Microglial Response? (Pubmed Central) - Mar 16, 2023
Moreover, many of these microglial proteins that are genetically associated with AD appear to interact and share pathways or regulatory mechanisms, presenting several points of convergence that may be strategic targets for therapeutic intervention. Here, we review some of these studies and their implications for microglial participation in AD pathogenesis.
- |||||||||| INHIBITION OF CD33-SIALIC ACID BINDING IN LATE-ONSET ALZHEIMER'S DISEASE (EXHIBITION) - Dec 23, 2022 - Abstract #ADPD2023ADPD_1421;
Sialic acid binding peptides were determined to inhibit CD33 binding to sialyated glycoproteins in vitro. Ongoing experiments aim to determine if inhibiting CD33 using sialic acid binding peptides is sufficient to resolve amyloid beta induced suppressed microglial immune signaling and increase microglial phagocytosis, response, and mitigate pathology.
- |||||||||| Journal: CD33 rs2455069 SNP: Correlation with Alzheimer's Disease and Hypothesis of Functional Role. (Pubmed Central) - Apr 19, 2022
Our analysis demonstrated that the CD33-R69G variant may bind sialic acid at additional binding sites compared to the wild type, thus potentially increasing its affinity/specificity for this molecule. Our results led to a new hypothesis of rs2455069-A>G SNP as a risk factor for AD, suggesting that a long-term cumulative effect of the CD33-R69G variant results from the binding of sialic acid, acting as an enhancer of the CD33 inhibitory effects on amyloid plaque degradation.
- |||||||||| cytarabine / Generic mfg.
Biomarker, Review, Journal: Role of Pharmacogenetics in the Treatment of Acute Myeloid Leukemia: Systematic Review and Future Perspectives. (Pubmed Central) - Mar 27, 2022
Plenteous pharmacogenetic studies have already been published for classical therapies, such as cytarabine or anthracyclines, but such studies remain scarce for newer drugs...A broad pharmacogenetic understanding may be useful in the design of dosing strategies and treatment guidelines. The aim of this study is to perform a review of the available publications and evidence related to the pharmacogenetics of AML, compiling those studies that may be useful in optimizing drug administration.
- |||||||||| Journal: The role of innate immune genes in Alzheimer's disease. (Pubmed Central) - Oct 20, 2021
We propose that hypoxia/ischemia, e.g., via the accumulation of sialylated gangliosides, prevents the phagocytosis of β-amyloid deposits by inhibiting CD33/TREM2 signaling. Targeting neuroinflammation via CD33 inhibition and/or TREM2 activation may have important implications for neurodegeneration in Alzheimer's disease and may be an addition to monoclonal anti-Aβ antibody treatments that remove plaques without reducing neuroinflammation.
- |||||||||| lirentelimab (AK002) / Allakos
Review, Journal: Discovery, Function, and Therapeutic Targeting of Siglec-8. (Pubmed Central) - Jul 14, 2021
AK002 administration has safely demonstrated the inhibition of mast cell activity and the depletion of eosinophils in several phase 1 and phase 2 trials. This article reviews the discovery and functions of Siglec-8, and strategies for its therapeutic targeting for the treatment of eosinophil- and mast cell-associated diseases.
- |||||||||| Journal, Myeloid-derived suppressor cells: HCV-Associated Exosomes Upregulate RUNXOR and RUNX1 Expressions to Promote MDSC Expansion and Suppressive Functions through STAT3-miR124 Axis. (Pubmed Central) - Jul 11, 2021
Conversely, silencing RUNXOR or RUNX1 expression in HCV-derived CD33 myeloid cells significantly inhibited their differentiation and expressions of suppressive molecules and improved the function of co-cultured autologous CD4 T cells. Taken together, these results indicate that the RUNXOR-RUNX1-STAT3-miR124 axis enhances the differentiation and suppressive functions of MDSCs and could be a potential target for immunomodulation in conjunction with antiviral therapy during chronic HCV infection.
- |||||||||| Zamyl (lintuzumab) / Seagen
Review, Journal: Targeted Alpha-Particle Therapy for Hematologic Malignancies. (Pubmed Central) - Jul 7, 2021
Initial studies showed that Bi-labeled lintuzumab had antileukemic activity and could produce remissions after partial cytoreduction with cytarabine...In a phase II study, treatment with Ac-lintuzumab monotherapy for a similar patient population resulted in remission in 69% of patients receiving two fractions of 74 kBq/kg and 22% of patients receiving two 55.5-kBq/kg fractions. Additionally, TAT may be useful in intensifying antileukemic therapy prior to hematopoietic cell transplantation, and pretargeting strategies offer the possibility for improved tumor-to-normal organ dose ratios.
- |||||||||| Review, Journal: Next-Generation Molecular Imaging of Thyroid Cancer. (Pubmed Central) - Jul 4, 2021
In this review, we summarize TC-targeting probes which include transporter-based and immuno-based imaging moieties. We summarize the most recent evidence in this field and outline how these emerging strategies may potentially optimize clinical practice.
- |||||||||| Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Review, Journal: CD33 Expression and Gentuzumab Ozogamicin in Acute Myeloid Leukemia: Two Sides of the Same Coin. (Pubmed Central) - Jul 4, 2021
The first "target therapy" to be introduced was the monoclonal anti-CD33 gemtuzumab ozogamicin (GO) in 2004...Cytogenetic, molecular, and immunophenotypic data are now able to predict the potential positive advantages of GO, with the exception of high-risk AML patients who do not seem to benefit. GO can be considered a 'repurposed drug' that could be beneficial for some patients with AML, mostly in combination with new drugs already approved or currently in testing.
- |||||||||| Journal: Role of Neuron and Glia in Alzheimer's Disease and Associated Vascular Dysfunction. (Pubmed Central) - Jul 3, 2021
Glial signals connect to neural stem cells, and a shift in glial phenotype over the AD trajectory even affects adult neurogenesis and the neurovascular niche. Overall, the current review informs about the interaction of neuronal and glial cell types in AD pathogenesis and its critical association with cerebrovascular dysfunction.
- |||||||||| Journal: Hyal2 expression in tumor-associated myeloid cells mediates cancer-related inflammation in bladder cancer. (Pubmed Central) - Jun 30, 2021
CD44-mediated signaling played an important role in the regulation of HA-degrading activity of Hyal2-expressing myeloid cells, as the engagement of CD44 receptor with specific monoclonal antibody triggered translocation of Hyal2 enzyme to the cellular surface and stimulated secretion of IL-1β. Taken together, this work identifies Hyal2-expressing tumor-associated myeloid cells as key players in the accumulation of LMW-HA in the tumor microenvironment and cancer-related inflammation and angiogenesis.
- |||||||||| Review, Journal: The Role of Siglec-G on Immune Cells in Sepsis. (Pubmed Central) - Jun 30, 2021
Here, we review the immunoregulatory functions of Siglec-G in B-1a cells and myeloid cells in sepsis. A clear understanding of Siglec-G is important to developing novel therapeutics in treating sepsis.
- |||||||||| clodronate disodium / Generic mfg.
Journal: Kidney residency of VISTA-positive macrophages accelerates repair from ischemic injury. (Pubmed Central) - Jun 22, 2021
To this end, mice without kidney-resident R1 macrophages but containing infiltrating monocyte-derived R2 macrophages were generated using differential cellular kinetics following clodronate liposome treatment...CD14 CD33 mononuclear phagocytes of human kidney also expressed VISTA, which has similar functions to the mouse counterpart. Thus, VISTA is upregulated in kidney macrophages in a tissue-dependent manner and plays a repair role during ischemic injury.
- |||||||||| melphalan / Generic mfg., fludarabine IV / Generic mfg., mycophenolate mofetil / Generic mfg.
Journal: Cord blood transplants supported by unrelated donor CD34 progenitor cells. (Pubmed Central) - Jun 22, 2021
Twenty-five received ATG and all received posttransplant tacrolimus and mycophenolate mofetil...Overall survival at 1 year was 54%. For patients in need of an alternative transplant who lack a haploidentical donor, haplo-cord transplantation using CD34-selected partially matched unrelated donor grafts results in rapid engraftment with no increased rate of cord graft failure or GVHD.
- |||||||||| Preclinical, Journal: Identification of aspartame-induced haematopoietic and lymphoid tumours in rats after lifetime treatment. (Pubmed Central) - Jun 8, 2021
A statistically significant increase in total HLTs (p = 0.006), total lymphomas (p = 0.032) and total leukaemias (p = 0.031) in treated female rats was confirmed (high dose vs control), and a statistically significant linear trend for each HLT type was also observed. After the HLT cases re-evaluation, the results obtained are consistent with those reported in the previous RI publication and reinforce the hypothesis that APM has a leukaemogenic and lymphomatogenic effect.
- |||||||||| Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Review, Journal, Adverse events: Prevention, recognition, and management of adverse events associated with gemtuzumab ozogamicin use in acute myeloid leukemia. (Pubmed Central) - Jun 8, 2021
Other non-specific serious adverse events (SAEs) associated with GO treatment are myelosuppression, bleeding/thrombocytopenia, infusion-related reaction, and tumor lysis syndrome. This report summarizes an expert panel of physicians' recommendations for the evaluation and management of SAEs following GO, emphasizing the prevention and management of VOD/SOS.
- |||||||||| Journal: Acute myeloid leukemia with mutated NPM1 mimics acute promyelocytic leukemia presentation. (Pubmed Central) - Jun 8, 2021
High WBC count and blasts with low to moderate side scatter and significant expression of CD4 are observed features that could assist in the differential diagnosis with APL. The occurrence of significant elevated D-dimer levels, or even overt DIC observed at diagnosis in these cases could be relevant for this AML subtype.
- |||||||||| Clinical, Journal: CD33 rs3865444 as a risk factor for Parkinson's disease. (Pubmed Central) - Jun 4, 2021
CD200 expression may exert its effect through upregulation of CTLA-4. The CD33 rs3865444 is associated with decreased PD risk, and larger studies investigating the role of CD33 rs3865444 on PD are needed.
- |||||||||| Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Clinical, Review, Journal: Clinical Pharmacology of Antibody-Drug Conjugates. (Pubmed Central) - Jun 3, 2021
Since the approval of first ADC (Gemtuzumab ozogamicin (trade name: Mylotarg)) for the treatment of CD33-positive acute myelogenous leukemia, several ADCs have been developed for the treatment of cancer...Unlike other small or large molecules where only one moiety and/or metabolite(s) is generally measured for the pharmacokinetic profiling, there are several moieties that need to be measured for characterizing the PK profiles of an ADC. Therefore, knowledge and understanding of clinical pharmacology of ADCs is vital for the selection of a safe and efficacious dose in a patient population.
- |||||||||| voriconazole / Generic mfg.
[VIRTUAL] FATAL DISSEMINATED INFECTION FROM FUSARIUM PROLIFERATUM IN A CHILD WITH ACUTE MYELOID LEUKEMIA () - Jun 2, 2021 - Abstract #ESPID2021ESPID_1435;
An 8-year-old boy with undifferentiated M0 AML, monosomy 7 and CD33 +, resistant in the initial treatment AML BFM 2004, MRD 50%, was treated with fludarabine, idarubicin, cytarabine and gemtuzumab-ozogamicin...The dose of voriconazole was increased to 15 mg/kg/day while liposomal amphotericin B was added at a dose of 5 mg/kg/day, simultaneously with antibiotics...are rare causes of invasive fungal infections, with very high mortality, in patients with hematological malignancies. Corticosteroid use and prolonged neutropenia are negative prognostic factors, while prophylactic use of antifungals seems not to be effective
- |||||||||| Clinical, Journal, IO biomarker: Tracing Leukemia Stem Cells and Their Influence on Clinical Course of Adult Acute Myeloid Leukemia. (Pubmed Central) - Jun 1, 2021
Corticosteroid use and prolonged neutropenia are negative prognostic factors, while prophylactic use of antifungals seems not to be effective Estimation of LSC expression is a sensitive indicator of the response to therapy in adult patients with AML and might be a better prognosticator than the findings from regular MRD panels.
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