A5049348778- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Viral Infectious Diseases and Gene Expression in Insects
- Biosimilars and Bioanalytical Methods
- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- Immunotherapy and Immune Responses
- Acute Myeloid Leukemia Research
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- X-ray Diffraction in Crystallography
- Glutathione Transferases and Polymorphisms
- Crystallization and Solubility Studies
- Advancements in Semiconductor Devices and Circuit Design
- SARS-CoV-2 and COVID-19 Research
- Chronic Lymphocytic Leukemia Research
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- Nitric Oxide and Endothelin Effects
- Lymphoma Diagnosis and Treatment
- Genomics, phytochemicals, and oxidative stress
Sidney Kimmel Comprehensive Cancer Center
2019-2025
Johns Hopkins University
2019-2025
Johns Hopkins Medicine
2019-2025
Bloomberg (United States)
2024-2025
University of Baltimore
2024
Sidney Kimmel Cancer Center
2023
Johns Hopkins Hospital
2020-2022
University of Michigan
2016-2021
Michigan Medicine
2017-2018
C. S. Mott Children's Hospital
2018
Background The prognosis of patients with recurrent/refractory acute myelogenous leukemia (AML) remains poor and cell-based immunotherapies hold promise to improve outcomes. Natural Killer (NK) cells can elicit an antileukemic response via a repertoire activating receptors that bind AML surface ligands. NK-cell adoptive transfer is safe but thus far has shown limited anti-AML efficacy. Here, we aimed overcome this limitation by engineering NK express chimeric antigen (CARs) boost their...
Cell therapies for solid tumors are thwarted by the hostile tumor microenvironment (TME) and heterogeneous expression of target antigens. We address both limitations with a novel class chimeric antigen receptors based on plant lectins, which recognize aberrant sugar residues that 'hallmark' malignant associated stromal cells. have expressed in T cells modified lectin from banana, H84T BanLec, attached to receptor (H84T-CAR) recognizes high-mannose (asparagine residue five nine mannoses)....
In an effort to identify genes whose expression is regulated by activated phosphatidylinositol 3-kinase (PI3K) signaling, we performed microarray analysis and subsequent quantitative reverse transcription-PCR on isogenic set of PTEN gene-targeted human cancer cells. Numerous p53 effectors were upregulated following deletion, including p21, GDF15, PIG3, NOXA, PLK2. Stable depletion led reversion the gene program. Western blots revealed that was stabilized in HCT116 PTEN(-/-) cells via...
Immunotherapy with CD123-specific T-cell engager proteins or T cells expressing chimeric antigen receptors is actively being pursued for acute myeloid leukemia. secreting bispecific molecules (ENG-T cells) may present a promising alternative to these approaches. To evaluate therapeutic potential, we generated secrete CD123/CD3-bispecific molecules. CD123-ENG recognized primary leukemia (AML) and cell lines in an antigen-dependent manner as judged by cytokine production and/or tumor killing,...
The literature provides evidence that metabolic nitric oxide (NO) release mediates the cytotoxic activities (against human leukemia and prostate cancer xenografts in mice) of JS-K, a compound structure R2N−N(O)NO−Ar for which R2N is 4-(ethoxycarbonyl)piperazin-1-yl Ar 2,4-dinitrophenyl. Here we present comparative data on potencies JS-K 41 other O2-arylated diazeniumdiolates as inhibitors HL-60 cell proliferation, well NCI 51-cell-line screen six them. show to be most potent 42 both screens...
Abstract T cells expressing chimeric antigen receptors (CARs) or the infusion of bispecific T-cell engagers (BITEs) have shown antitumor activity in humans for CD19-positive malignancies. While BITEs redirect large reservoir resident to tumors, CAR rely on significant vivo expansion exert activity. We that it is feasible modify secrete solid tumor antigen-specific BITEs, enabling cells. To adapt this approach malignancies we now generated secretable, CD19-specific (CD19-ENG cells). CD19-ENG...
Background Natural Killer (NK) cells have intrinsic anticancer activity that can be redirected toward acute myeloid leukemia (AML) with chimeric antigen receptor (CAR) engineering. Here, we study the functional consequences of CAR binding affinity and targeted epitope on CAR-NK cell activation, cytolytic synapse formation, antitumor activity. Methods We characterized NK-92 primary NK populations expressing variant AML-specific CARs containing single-chain variable fragments (scFvs, 26292 or...
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Ions of structure R2N[N(O)NO]- and their alkylation products have seen increasing use as nitric oxide (NO)-generating agents for biomedical research applications. Here we show that such diazeniumdiolate anions can readily displace halide from a variety electrophilic aza- or nitroaromatic substrates to form O2-arylated derivatives R2N−N(O)N−OAr. The site arylation the cis arrangement oxygens were confirmed by X-ray crystallography. Displacement various nucleophiles showed be reasonably good...
CD19-specific chimeric antigen receptor (CAR) T-cell therapies, including the FDA–approved tisagenlecleucel, induce high rates of remission in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, post-treatment relapse remains an issue. Optimal management B-ALL after tisagenlecleucel treatment elusive, and continued tracking outcomes is necessary to establish a standard care for this population. We sought evaluate on real-world use contemporary...
Abstract Development of chemotherapeutic resistance is a major cause pharmacologic failure in cancer treatment. One mechanism tumor cells the overexpression glutathione S-transferases (GSTs) that serve two distinct roles development drug via formation conjugates with drugs for their cellular efflux, and inhibition mitogen-activated protein kinase pathway. To target GST-based to chemotherapeutics, series nitric oxide (NO)-releasing diazeniumdiolates was synthesized shown release NO on...
H84T-Banana Lectin (BanLec) CAR-NK cells bind high mannose glycosites that decorate the SARS-CoV-2 envelope, thereby decreasing cellular infection in a model of SARS-CoV-2. H84T-BanLec are innate effector cells, activated by virus. This novel agent is promising therapeutic, capable clearing circulating virus and infected cells. Banana binds glycans on viral envelopes, exerting an anti-viral effect. A point mutation (H84T) divorces BanLec mitogenicity from antiviral activity. contains...
The identification of new pathways supporting the myelodysplastic syndrome (MDS) primitive cells growth is required to develop targeted therapies. Within myeloid malignancies, men have worse outcomes than women, suggesting male sex hormone–driven effects in malignant hematopoiesis. Androgen receptor promotes expression five granulocyte colony-stimulating factor receptor–regulated genes. Among them, CCRL2 encodes an atypical chemokine regulating cytokine signaling granulocytes, but its role...