A5026191929- CAR-T cell therapy research
- Biosimilars and Bioanalytical Methods
- Cancer, Hypoxia, and Metabolism
- Biochemical and Molecular Research
- Cancer-related Molecular Pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Metal complexes synthesis and properties
- RNA modifications and cancer
- Chronic Lymphocytic Leukemia Research
- Autophagy in Disease and Therapy
- interferon and immune responses
- Integrated Circuits and Semiconductor Failure Analysis
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Cancer therapeutics and mechanisms
- Cancer Research and Treatments
- Endoplasmic Reticulum Stress and Disease
- CNS Lymphoma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Virus-based gene therapy research
- Advanced biosensing and bioanalysis techniques
- Prostate Cancer Treatment and Research
- Colorectal Cancer Treatments and Studies
Kite (United States)
2023-2024
University of California, Los Angeles
2014-2022
Molecular Theranostics (United States)
2022
Imaging Center
2020
UCLA Health
2018-2019
APLA Health
2019
Indian Institute of Technology Kharagpur
2014
Trinity College Dublin
2011
Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel patients with R/R indolent non-Hodgkin (iNHL; N = 104), including FL and marginal zone (MZL). In primary analysis (median follow-up, 17.5 months), overall response rate (ORR) 92% (complete rate, 74%). Here, we report long-term outcomes...
Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target cancer. PET probes for dCK have been developed are effective mice but suboptimal specificity sensitivity humans. To identify more suitable probe clinical imaging, we compared selectivity of two candidate compounds-[(18)F]Clofarabine; 2-chloro-2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-adenine...
Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia Rad3-related protein (ATR) reduces output both salvage pathways by regulating activity their respective rate-limiting enzymes, ribonucleotide reductase (RNR) deoxycytidine (dCK), via distinct molecular mechanisms....
Significance Pancreatic cancer is notoriously treatment resistant. These tumors rely on lysosome-dependent recycling pathways to generate substrates for metabolism, which are inhibited by chloroquine (CQ) and its derivatives. However, clinical efficacy of CQ as a monotherapy or combined with standard-of-care regimens has been limited. Using an unbiased kinome screen, we identify replication stress induced vulnerability due impaired de novo nucleotide biosynthesis find that combination...
Treatment resistance and toxicities remain a risk following chimeric antigen receptor (CAR) T-cell therapy. Herein, we report pharmacokinetics, pharmacodynamics, product apheresis attributes associated with outcomes among patients relapsed/refractory large B-cell lymphoma (LBCL) treated axicabtagene ciloleucel (axi-cel) in ZUMA-7. Axi-cel peak expansion clinical response toxicity, but not durability. In material final product, naive phenotype (CCR7+CD45RA+) expressing CD27 CD28 improved...
2006 Background: Prognosis of patients with relapsed/refractory (R/R) CNSL is poor no standard care treatment options. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel) has shown efficacy in R/R systemic large B-cell lymphoma (LBCL) and could be considered for CNSL. Methods: We conducted a pilot study axi-cel CNS LBCL. No bridging except corticosteroids was allowed after enrollment. Ommaya reservoir placed before infusion. Patients underwent...
The influence of isotopically enriched magnesium on the creatine kinase catalyzed phosphorylation adenosine diphosphate is examined in two independent series experiments where triphosphate (ATP) concentrations were determined by a luciferase-linked luminescence end-point assay or real-time spectrophotometric assay. No increase was observed between rates ATP production with natural Mg, 24 and 25 nor any significant magnetic field effect fields from 3 to 1,000 mT. Our results are conflict...
Nine arsenic (As)-resistant bacterial strains isolated from As-rich groundwater samples of West Bengal were characterized to elucidate their potential in geomicrobial transformation and bioremediation aspects. The 16S rRNA gene-based phylogenetic analysis revealed that the affiliated with genera Actinobacteria, Microbacterium, Pseudomonas Rhizobium. exhibited high resistance As [Minimum inhibitory concentration (MIC) ≥ 10 mM As3+ MIC 450 As5+] other heavy metals, e.g., Cu2+, Cr2+, Ni2+, etc....
Clinical <sup>177</sup>Lu-PSMA-617 radioligand therapy (RLT) is applied in advanced-stage prostate cancer. However, to the best of our knowledge murine models study biologic effects various activity levels have not been established. The aim this was optimize specific and total for RLT a syngeneic model <b>Methods:</b> Murine-reconstituted, oncogene-driven cancer cells (0.1 × 10<sup>6</sup>) (RM1), transduced express human prostate-specific membrane antigen (PSMA), were injected into left...
We determine that type I interferon (IFN) response biomarkers are enriched in a subset of pancreatic ductal adenocarcinoma (PDAC) tumors; however, actionable vulnerabilities associated with IFN signaling have not been systematically defined. Integration phosphoproteomic analysis and chemical genomics synergy screen reveals activates the replication stress kinase ataxia telangiectasia Rad3-related protein (ATR) PDAC cells sensitizes them to ATR inhibitors. triggers cell-cycle arrest S-phase,...
Arginine (Arg) deprivation is a promising therapeutic approach for tumors with low argininosuccinate synthetase 1 (ASS1) expression. However, its efficacy as single agent therapy needs to be improved resistance frequently observed. Methods: A tissue microarray was performed assess ASS1 expression in surgical specimens of pancreatic ductal adenocarcinoma (PDAC) and correlation disease prognosis. An RNA-Seq analysis examined the role regulating global gene transcriptome. high throughput screen...
Ac-PSMA-617 targeted-therapy has demonstrated efficacy in 75-85% of patients; however, responses are not durable. We aimed to establish translatable mouse models disseminated prostate cancer (PCa) evaluate effectiveness
Significance A hallmark of pancreatic ductal adenocarcinoma (PDAC) is its extensively reprogrammed metabolic network, in which NAD and reduced form NADH are critical cofactors. Here, we show that IFN signaling, present a subset PDAC tumors, increases consumption NAD(H) through upregulation PARP9, PARP10, PARP14. This results increased dependence upon NAMPT for the recycling NAM to salvage pools, thus sensitizing these tumor cells treatment with pharmacologic inhibition by decreasing cell...
Biosynthesis of the pyrimidine nucleotide uridine monophosphate (UMP) is essential for cell proliferation and achieved by activity convergent de novo salvage metabolic pathways. Here we report development application a cell-based modifier screening platform that leverages redundancy in metabolism discovery selective UMP biosynthesis modulators. In evaluating library protein kinase inhibitors, identified multiple compounds possess modifying activity. The JNK inhibitor JNK-IN-8 was found to...
Recently, we have shown that small molecule dCK inhibitors in combination with pharmacological perturbations of de novo dNTP biosynthetic pathways could eliminate acute lymphoblastic leukemia cells animal models. However, our previous lead compound had a short half-life vivo. Therefore, set out to develop favorable pharmacokinetic properties. We delineated the sites inhibitor for modification, guided by crystal structures complex and derivatives. Crystal structure between racemic mixture new...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in United States, with an overall survival less than one year. An improved knowledge PDAC biology, to uncover vulnerabilities specific cancer cells, needed develop more effective therapeutic options. We are investigating intersection between three aspects biology that can, ultimately, be developed for therapeutics: (i) cytokine signaling, a particular focus on metabolic effects interferons...
A potent class of isoquinoline-based α-N-heterocyclic carboxaldehyde thiosemicarbazone (HCT) compounds has been rediscovered; based upon this scaffold, three series antiproliferative agents were synthesized through iterative rounds methylation and fluorination modifications, with anticancer activities being potentiated by physiologically relevant levels copper. The lead compound, HCT-13, was highly against a panel pancreatic, small cell lung carcinoma, prostate cancer, leukemia models, IC50...