A5079791833- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- NF-κB Signaling Pathways
- Kruppel-like factors research
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Biosimilars and Bioanalytical Methods
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- interferon and immune responses
- Peptidase Inhibition and Analysis
- Genetic factors in colorectal cancer
- Cytokine Signaling Pathways and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Immune Cell Function and Interaction
- Integrated Circuits and Semiconductor Failure Analysis
- Ovarian cancer diagnosis and treatment
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Mechanisms of cancer metastasis
Kite (United States)
2023-2025
Gilead Sciences (France)
2024
Atara Biotherapeutics (United States)
2019-2020
University of Southampton
2018
Peter MacCallum Cancer Centre
2018
Memorial Sloan Kettering Cancer Center
2018
Mayo Clinic in Arizona
2018
University of Cambridge
2018
QIMR Berghofer Medical Research Institute
2018
Mayo Clinic in Florida
2018
Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). Outcomes after a 3-year follow-up in pivotal ZUMA-2 study KTE-X19 MCL are reported, including subgroups by prior (bendamustine and type Bruton tyrosine kinase inhibitor [BTKi]) or high-risk characteristics.Patients with (one to five therapies, BTKi exposure) received single infusion (2 × 106 CAR T...
In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at years in patients with refractory large B-cell lymphoma (LBCL). Here, we aimed to assess survival and safety ZUMA-1 after 5 follow-up. Eligible adults LBCL (diffuse lymphoma, primary mediastinal transformed follicular lymphoma) received lymphodepleting chemotherapy followed by axi-cel...
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...
Abstract The phase 3 ZUMA-7 trial in second-line large B cell lymphoma demonstrated superiority of anti-CD19 CAR T therapy (axicabtagene ciloleucel (axi-cel)) over standard care (SOC; salvage chemotherapy followed by hematopoietic transplantation) ( NCT03391466 ). Here, we present a prespecified exploratory analysis examining the association between pretreatment tumor characteristics and efficacy axi-cel versus SOC. gene expression signature (GES) CD19 associated significantly with improved...
Although the roles of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling in KRAS-driven tumorigenesis are well established, KRAS activates additional pathways required for tumor maintenance, inhibition which likely to be necessary effective KRAS-directed therapy. Here, we show that IκB (IKK)-related kinases Tank-binding kinase-1 (TBK1) IKKε promote by regulating autocrine CCL5 interleukin (IL)-6 identify CYT387 as a potent JAK/TBK1/IKKε inhibitor....
Chimeric antigen receptor T (CAR-T) cell therapy is limited by cytokine release syndrome (CRS) and neurotoxicity (NT). We sought to use once-daily prophylactic anakinra, an IL-1R antagonist, prevent CRS/NT that would require hospitalization (grade 2 or higher) in patients receiving axicabtagene ciloleucel for large lymphoma, with the goal of facilitating outpatient management. Our study (ClinicalTrials.gov #NCT04150913), line others, demonstrated anakinra insufficient development toxicities...
Cell transformation assays (CTAs) have long been proposed as in vitro methods for the identification of potential chemical carcinogens. Despite showing good correlation with rodent bioassay data, concerns over subjective nature using morphological criteria identifying transformed cells and a lack understanding mechanistic basis has limited their acceptance regulatory purposes. However, recent drivers to find alternative carcinogenicity assessment methodologies, such Seventh Amendment EU...
3q26 is frequently amplified in several cancer types with a common region containing 20 genes. To identify driver genes this region, we interrogated the function of each these by loss- and gain-of-function genetic screens. Specifically, found that TLOC1 (SEC62) was selectively required for proliferation cell lines amplification. Increased expression induced anchorage-independent growth, second gene, SKIL (SNON), facilitated invasion immortalized human mammary epithelial cells. Expression...
Abstract ZUMA-1 safety management cohort 6 investigated the impact of prophylactic corticosteroids and earlier and/or tocilizumab on incidence severity cytokine release syndrome (CRS) neurologic events (NEs) following axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). Prior analyses limited follow-up demonstrated no Grade ≥3 CRS, a low rate NEs, high response rates, without negatively impacting axi-cel pharmacokinetics. Herein, long-term...
IκB kinase ε (IKKε, IKBKE) is a key regulator of innate immunity and breast cancer oncogene, amplified in ∼30% cancers, that promotes malignant transformation through NF-κB activation. Here, we show IKKε modified regulated by K63-linked polyubiquitination at lysine 30 401. Tumor necrosis factor alpha interleukin-1β stimulation induces over baseline levels both macrophages cell lines, this modification essential for activity, IKKε-mediated activation, IKKε-induced transformation. Disruption...
NF-κB transcription factors are central regulators of inflammation and when dysregulated contribute to malignant transformation. IκB kinase ε (IKKε; IKKi, encoded by IKBKE) is a breast oncogene that amplified in 30% cancers drives transformation an NF-κB-dependent manner. Here we demonstrate IKKε interacts with phosphorylates tumor necrosis factor receptor-associated 2 (TRAF2) at Ser11 vitro vivo. This activity promotes Lys63-linked TRAF2 ubiquitination activation essential for Breast cancer...
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...