A5032774787- CAR-T cell therapy research
- Cancer Research and Treatments
- Virus-based gene therapy research
- Glioma Diagnosis and Treatment
- Functional Brain Connectivity Studies
- Dementia and Cognitive Impairment Research
- Cancer Immunotherapy and Biomarkers
- Retinoids in leukemia and cellular processes
- Alzheimer's disease research and treatments
- CRISPR and Genetic Engineering
- Lymphoma Diagnosis and Treatment
- Advanced Neuroimaging Techniques and Applications
- Sarcoma Diagnosis and Treatment
- Health, Environment, Cognitive Aging
- Vascular Tumors and Angiosarcomas
- Frailty in Older Adults
- Tryptophan and brain disorders
- Genetics, Aging, and Longevity in Model Organisms
- Neonatal and fetal brain pathology
- Bioinformatics and Genomic Networks
- Down syndrome and intellectual disability research
- Neurological Disease Mechanisms and Treatments
- Emotional Labor in Professions
- Intracerebral and Subarachnoid Hemorrhage Research
- Cardiac tumors and thrombi
Center for Inherited Blood Disorders
2022
Indiana University – Purdue University Indianapolis
2022
Ziopharm Oncology (United States)
2008-2021
Indiana University Bloomington
2019-2021
Boston University
2019-2021
Institut Bergonié
2016
Centre Léon Bérard
2016
Northwestern University
2008
Human interleukin-12 (hIL-12) is a cytokine with anticancer activity, but its systemic application limited by toxic inflammatory responses. We assessed the safety and biological effects of an hIL-12 gene, transcriptionally regulated oral activator. A multicenter phase 1 dose-escalation trial (NCT02026271) treated 31 patients undergoing resection recurrent high-grade glioma. Resection cavity walls were injected (day 0) fixed dose vector (Ad-RTS-hIL-12). The activator for hIL-12, veledimex...
Purpose Palifosfamide is the active metabolite of ifosfamide and does not require prodrug activation, thereby avoiding generation toxic metabolites. The PICASSO III trial compared doxorubicin plus palifosfamide with placebo in patients who had received no prior systemic therapy for metastatic soft tissue sarcoma. Patients Methods were randomly assigned 1:1 to receive 75 mg/m2 intravenously day 1 150 mg/m2/d days 3 or once every 21 up six cycles. primary end point was progression-free...
Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near central nervous system (CNS) parenchyma2, their role CNS physiology has not been sufficiently well studied. Given continuous interaction with cerebrospinal fluid (CSF) strategic positioning, we refer to these cells collectively as parenchymal border (PBMs). Here demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation express high levels...
Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against pathology, its effect on tau pathology and potential beneficial role people with disease still unclear. Our aim was study associations between dynamics soluble TREM2, as a biomarker signalling, amyloid β (Aβ) deposition, tau-related neuroimaging markers, cognitive decline,...
Abstract Background Veledimex (VDX)-regulatable interleukin-12 (IL-12) gene therapy in recurrent glioblastoma (rGBM) was reported to show tumor infiltration of CD8+ T cells, encouraging survival, but also up-regulation immune checkpoint signaling, providing the rationale for a combination trial with inhibition. Methods An open-label, multi-institutional, dose-escalation phase I rGBM subjects (NCT03636477) accrued 21 3 dose-escalating cohorts: (1) neoadjuvant then ongoing nivolumab (1mg/kg)...
"Brain-predicted age" quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted has been well established in symptomatic Alzheimer disease (AD), but is underexplored preclinical AD. Prior studies have typically used structural MRI, resting-state functional connectivity (FC) remains underexplored. Our model predicted from FC 391 cognitively normal, amyloid-negative controls (ages 18-89). We applied the trained 145 amyloid-negative, 151 AD, and 156...
This study examined the relationships of social stressors arising from interactions with civilians and suspects (outsiders) coworkers supervisors (insiders) turnover intention, psychological distress, emotional exhaustion. It also surface acting—a way faking appropriate emotions—as a mediator these relationships. Using online survey data collected 196 police officers, authors found that both sources were related to all three outcomes acting mediated These results extend literature on labor...
<h3>Importance</h3> Allelic variation in the brain-derived neurotrophic factor (<i>BDNF</i>) Val66Met polymorphism moderates increases cerebrospinal fluid (CSF) levels of tau and phosphorylated 181 (p-tau181), measured using immunoassay, cognitive decline presymptomatic dominantly inherited Alzheimer disease (DIAD). Advances mass spectrometry show that CSF phosphorylation occupancy at threonine 217 (p-tau181/tau181, p-tau217/tau217) with initial β-amyloid (Aβ) aggregation, while 205...
Abstract Neurofilament light chain, a putative measure of neuronal damage, is measurable in blood and CSF predictive cognitive function individuals with Alzheimer’s disease. There has been limited prior work linking neurofilament functional connectivity, no investigated associations connectivity autosomal dominant Here, we assessed relationships between light, cognition, cross-sectional sample 106 disease mutation carriers 76 non-carriers. We employed an innovative network-level enrichment...
Abstract Background PSEN1, PSEN2, and APP mutations cause Alzheimer’s disease (AD) with an early age at onset (AAO) progressive cognitive decline. PSEN1 are more common generally have earlier AAO; however, certain a later AAO, similar to those observed in PSEN2 . Methods We examined whether endotypes exist across these AAO (~ 55 years) using hiPSC-derived neurons from familial (FAD) patients harboring A79V , N141I V717I mechanistically characterized by integrating RNA-seq ATAC-seq. Results...
Abstract Structural grey matter covariance networks provide an individual quantification of morphological patterns in the brain. The network integrity is disrupted sporadic Alzheimer’s disease, and properties show associations with level amyloid pathology cognitive decline. Therefore, these might be disease progression markers. However, it remains unclear when how changes progression. We investigated questions autosomal dominant mutation carriers, whose conserved age at dementia onset allows...
10004 Background: Palifosfamide (ZIO-201) references a novel DNA cross-linking composition that comprises the functional active metabolite of ifosfamide (IFOS). It lacks hemorrhagic cystitis and CNS toxicity IFOS. has broad activity in human sarcoma xenograft models is IFOS-resistant xenografts. This study randomized Phase II trial evaluating safety efficacy combination palifosfamide + doxorubicin vs. alone patients with metastatic/unresectable first- second-line soft tissue (STS). Methods:...
We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer's disease patient-derived iPSC harbouring PSEN1 H163R mutation. This demonstrates morphology, expression pluripotency markers, and maintains normal karyotype.
2044 Background: Glioblastoma (GBM) is an aggressive brain tumor affecting ~74,000 people worldwide annually. Recurrent GBM patients have a median OS (mOS) of 6-7 months. in who failed temozolomide, bevacizumab or equivalent salvage chemotherapy, ~3-5 New therapies are urgently needed. Ad-RTS-hIL-12 (Ad) novel gene therapy expressing IL-12 under the control oral activator ligand, veledimex (V), through RheoSwitch Therapeutic System. Intratumoral administration Ad results targeted...
2020 Background: Ad-RTS-hIL-12 (Ad) is a novel gene therapy candidate conditionally expressing IL-12 under the control of veledimex (V) acting via proprietary RheoSwitch Therapeutic System (RTS) switch with therapeutic window. Intratumoral Ad + oral V monotherapy (Phase 1 study, NCT02026271 ) resulted in new sustained intra-tumor influx activated cytotoxic T cells, consistent an immune-mediated anti-tumor effect improving median overall survival (mOS) subjects recurrent glioblastoma (rGBM)....
Abstract Ad-RTS-hIL-12(Ad) is a gene therapy candidate conditionally expressing IL-12 under the transcriptional control of veledimex(V) acting via RheoSwitch Therapeutic System® switch. Veledimex plasma and tumor PK demonstrated dose-response relationship crossing BBB. PD-1+ T-cells were increased in biopsy samples after treatment with Controlled-IL-12 phase-l study. This finding was rationale for conducting 2 trials combination PD-1-inhibitor to enhance T-cell-mediated anti-tumor effects....
3038 Background: Ad-RTS-hIL-12 (Ad) is a novel gene therapy candidate expressing IL-12 under the control of an orally administered activator ligand, veledimex (V), through proprietary RheoSwitch Therapeutic System (RTS) switch. This platform reduces systemic toxicity and stimulates anti-cancer T cell immune response. Methods: Two open label trials evaluated tolerability local inducible expression in heavily pretreated patients with metastatic breast cancer (mBC) or recurrent glioblastoma...
2510 Background: Monotherapy with intratumoral Ad-RTS-hIL-12 (Ad), a gene therapeutic conditionally expressing IL-12 under the transcriptional control of oral veledimex (“Controlled IL-12”), was shown in phase 1 study (NCT02026271) to elicit new and sustained intra-tumoral infiltration T cells co-expression PD-1. We report updated findings following completion enrollment (with follow-up ongoing) for substudy (NCT03636477) evaluating safety tolerability local, Controlled combination nivolumab...
Ad-RTS-hIL-12 (Ad) is a novel gene therapy expressing IL-12 via the RheoSwitch Therapeutic System® switch under control of an oral activator ligand, veledimex (V). We previously reported on open label Phase I trial describing biological activity recombinant with downstream IFN-γ and activation immune system. provide update intratumoral injections Ad (2x1011virus-particles) + V for patients recurrent GBM (rGBM) in Group 1 (G1) (craniotomy, n=31) initial results 2 (G2) (stereotactic...