23 results on '"Desseaux C"'
Search Results
2. Gene transfer of integration defective anti-HSV-1 meganuclease to human corneas ex vivo
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Elbadawy, H M, Gailledrat, M, Desseaux, C, Salvalaio, G, Di Iorio, E, Ferrari, B, Bertolin, M, Barbaro, V, Parekh, M, Gayon, R, Munegato, D, Franchin, E, Calistri, A, Palù, G, Parolin, C, Ponzin, D, and Ferrari, S
- Published
- 2014
- Full Text
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3. The I-CreI meganuclease and its engineered derivatives: applications from cell modification to gene therapy
- Author
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Arnould, S., Delenda, C., Grizot, S., Desseaux, C., Pâques, F., Silva, G.H., and Smith, J.
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- 2011
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4. P05.05 Safety and feasibility of temporary blood-brain barrier disruption with the SonoCloud-1/3 implantable ultrasound device in recurrent glioblastoma
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Idbaih, A, primary, Canney, M, additional, Bouchoux, G, additional, Desseaux, C, additional, Vignot, A, additional, Lafon, C, additional, Chapelon, J, additional, Delattre, J, additional, Belin, L, additional, and Carpentier, A, additional
- Published
- 2019
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5. Gene transfer of HSV1-specific meganuclease to the murine cornea
- Author
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ROUSSEAU, A, primary, ERGANI, A, additional, GABISON, E, additional, CORRAL, M, additional, GAILLEDRAT, M, additional, DESSEAUX, C, additional, ROY, P, additional, CHAPELLIER, B, additional, and LABETOULLE, M, additional
- Published
- 2012
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6. Meganuclease‐mediated inhibition of HSV1 infection
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LABETOULLE, M, primary, HUOT, N, additional, SMITH, J, additional, GROSSE, S, additional, BARRADEAU, S, additional, ARNOULD, S, additional, MAHIET, C, additional, DESSEAUX, C, additional, CEDRONE, F, additional, PAQUES, F, additional, CHAPELLIER, BC, additional, GABISON, EE, additional, and ERGANI, A, additional
- Published
- 2011
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7. The I-CreI meganuclease and its engineered derivatives: applications from cell modification to gene therapy
- Author
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Arnould, S., primary, Delenda, C., additional, Grizot, S., additional, Desseaux, C., additional, Paques, F., additional, Silva, G. H., additional, and Smith, J., additional
- Published
- 2010
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8. ChemInform Abstract: Synthesis and Properties of Phosphodiester and Triester Derivatives of AZT with Tethered Potential Ribonucleases.
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DESSEAUX, C., primary, GOUYETTE, C., additional, HENIN, Y., additional, and HUYNH-DINH TAM, HUYNH-DINH TAM, additional
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- 2010
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9. ChemInform Abstract: Synthesis and Properties of Phosphodiester and Triester Derivatives of AZT with Tethered Potential Ribonucleases.
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DESSEAUX, C., GOUYETTE, C., HENIN, Y., and HUYNH-DINH TAM, HUYNH-DINH TAM
- Published
- 1995
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10. Formation of nitrogen oxides including NO from oxidative cleavage of C=N(OH) bonds: a general cytochrome P450-dependent reaction
- Author
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Jousserandot, A., Boucher, J.-L., Desseaux, C., and Delaforge, M.
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- 1995
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11. Synthesis of phosphodiester and triester derivatives of AZT with tethered N-methyl piperazine and N,N,N'-trimethylethylenediamine
- Author
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Desseaux, C. and Huynh-Dinh, T.
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- 1993
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12. Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas.
- Author
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Arrieta VA, Gould A, Kim KS, Habashy KJ, Dmello C, Vázquez-Cervantes GI, Palacín-Aliana I, McManus G, Amidei C, Gomez C, Dhiantravan S, Chen L, Zhang DY, Saganty R, Cholak ME, Pandey S, McCord M, McCortney K, Castro B, Ward R, Muzzio M, Bouchoux G, Desseaux C, Canney M, Carpentier A, Zhang B, Miska JM, Lesniak MS, Horbinski CM, Lukas RV, Stupp R, Lee-Chang C, and Sonabend AM
- Subjects
- Animals, Humans, Mice, Cell Line, Tumor, Glioma drug therapy, Glioma immunology, Glioma pathology, Brain metabolism, Brain drug effects, Female, Drug Delivery Systems, Ultrasonic Waves, Glioblastoma drug therapy, Glioblastoma immunology, Glioblastoma pathology, Male, Microglia drug effects, Microglia metabolism, Mice, Inbred C57BL, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized pharmacology, Immune Checkpoint Inhibitors pharmacology, Immune Checkpoint Inhibitors administration & dosage, Polyethylene Glycols, Doxorubicin pharmacology, Doxorubicin administration & dosage, Doxorubicin therapeutic use, Doxorubicin analogs & derivatives, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor metabolism, Blood-Brain Barrier metabolism, Blood-Brain Barrier drug effects, Brain Neoplasms drug therapy, Brain Neoplasms immunology, Brain Neoplasms pathology, Microbubbles
- Abstract
Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM., (© 2024. The Author(s).)
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- 2024
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13. Repeated blood-brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial.
- Author
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Carpentier A, Stupp R, Sonabend AM, Dufour H, Chinot O, Mathon B, Ducray F, Guyotat J, Baize N, Menei P, de Groot J, Weinberg JS, Liu BP, Guemas E, Desseaux C, Schmitt C, Bouchoux G, Canney M, and Idbaih A
- Subjects
- Humans, Carboplatin adverse effects, Ultrasonography, Biological Transport, Antineoplastic Combined Chemotherapy Protocols adverse effects, Blood-Brain Barrier pathology, Glioblastoma diagnostic imaging, Glioblastoma drug therapy
- Abstract
Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion. The primary objective of the Phase 1 was to evaluate the safety of escalating numbers of ultrasound emitters using a standard 3 + 3 dose escalation. The primary objective of the Phase 2 was to evaluate the efficacy of BBB opening using magnetic resonance imaging (MRI). The secondary objectives included safety and clinical efficacy. Thirty-three patients received a total of 90 monthly sonications with carboplatin administration and up to nine emitters activated without observed DLT. Grade 3 procedure-related adverse events consisted of pre syncope (n = 3), fatigue (n = 1), wound infection (n = 2), and pain at time of device connection (n = 7). BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival rate was 58% and median overall survival was 14.0 months from surgery., (© 2024. The Author(s).)
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- 2024
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14. Advances in Blood-Brain Barrier Disruption to Facilitate Drug Delivery for Infiltrative Gliomas.
- Author
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Gould A, Gonzales VAA, Dmello CC, Saganty R, Lukas RV, Zhang DY, Heimberger AB, Canney M, Carpentier A, Desseaux C, Bouchoux G, Stupp R, and Sonabend AM
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- 2023
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15. Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial.
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Sonabend AM, Gould A, Amidei C, Ward R, Schmidt KA, Zhang DY, Gomez C, Bebawy JF, Liu BP, Bouchoux G, Desseaux C, Helenowski IB, Lukas RV, Dixit K, Kumthekar P, Arrieta VA, Lesniak MS, Carpentier A, Zhang H, Muzzio M, Canney M, and Stupp R
- Subjects
- Adult, Male, Humans, Female, Adolescent, Albumin-Bound Paclitaxel adverse effects, Carboplatin, Blood-Brain Barrier, Paclitaxel, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Glioblastoma diagnostic imaging, Glioblastoma drug therapy, Brain Diseases chemically induced, Brain Diseases drug therapy
- Abstract
Background: Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood-brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma., Methods: We conducted a dose-escalation phase 1 clinical trial in adults (aged ≥18 years) with recurrent glioblastoma, a tumour diameter of 70 mm or smaller, and a Karnofsky performance status of at least 70. A nine-emitter ultrasound device was implanted into a skull window after tumour resection. LIPU-MB with intravenous albumin-bound paclitaxel infusion was done every 3 weeks for up to six cycles. Six dose levels of albumin-bound paclitaxel (40 mg/m
2 , 80 mg/m2 , 135 mg/m2 , 175 mg/m2 , 215 mg/m2 , and 260 mg/m2 ) were evaluated. The primary endpoint was dose-limiting toxicity occurring during the first cycle of sonication and albumin-bound paclitaxel chemotherapy. Safety was assessed in all treated patients. Analyses were done in the per-protocol population. Blood-brain barrier opening was investigated by MRI before and after sonication. We also did pharmacokinetic analyses of LIPU-MB in a subgroup of patients from the current study and a subgroup of patients who received carboplatin as part of a similar trial (NCT03744026). This study is registered with ClinicalTrials.gov, NCT04528680, and a phase 2 trial is currently open for accrual., Findings: 17 patients (nine men and eight women) were enrolled between Oct 29, 2020, and Feb 21, 2022. As of data cutoff on Sept 6, 2022, median follow-up was 11·89 months (IQR 11·12-12·78). One patient was treated per dose level of albumin-bound paclitaxel for levels 1 to 5 (40-215 mg/m2 ), and 12 patients were treated at dose level 6 (260 mg/m2 ). A total of 68 cycles of LIPU-MB-based blood-brain barrier opening were done (median 3 cycles per patient [range 2-6]). At a dose of 260 mg/m2 , encephalopathy (grade 3) occurred in one (8%) of 12 patients during the first cycle (considered a dose-limiting toxicity), and in one other patient during the second cycle (grade 2). In both cases, the toxicity resolved and treatment continued at a lower dose of albumin-bound paclitaxel, with a dose of 175 mg/m2 in the case of the grade 3 encephalopathy, and to 215 mg/m2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m2 albumin-bound paclitaxel. No progressive neurological deficits attributed to LIPU-MB were observed. LIPU-MB-based blood-brain barrier opening was most commonly associated with immediate yet transient grade 1-2 headache (12 [71%] of 17 patients). The most common grade 3-4 treatment-emergent adverse events were neutropenia (eight [47%]), leukopenia (five [29%]), and hypertension (five [29%]). No treatment-related deaths occurred during the study. Imaging analysis showed blood-brain barrier opening in the brain regions targeted by LIPU-MB, which diminished over the first 1 h after sonication. Pharmacokinetic analyses showed that LIPU-MB led to increases in the mean brain parenchymal concentrations of albumin-bound paclitaxel (from 0·037 μM [95% CI 0·022-0·063] in non-sonicated brain to 0·139 μM [0·083-0·232] in sonicated brain [3·7-times increase], p<0·0001) and carboplatin (from 0·991 μM [0·562-1·747] in non-sonicated brain to 5·878 μM [3·462-9·980] μM in sonicated brain [5·9-times increase], p=0·0001)., Interpretation: LIPU-MB using a skull-implantable ultrasound device transiently opens the blood-brain barrier allowing for safe, repeated penetration of cytotoxic drugs into the brain. This study has prompted a subsequent phase 2 study combining LIPU-MB with albumin-bound paclitaxel plus carboplatin (NCT04528680), which is ongoing., Funding: National Institutes of Health and National Cancer Institute, Moceri Family Foundation, and the Panattoni family., Competing Interests: Declaration of interests AMS and RS have received in-kind (drug) support from Bristol-Myers Squibb, in-kind (ultrasound devices) and research support from and Carthera, and in-kind (drug) and research support from Agenus. AMS, DYZ, VAA, and RS are co-authors of intellectual property filed by Northwestern University related to therapeutic ultrasound. RS has acted or is acting as a scientific advisor or has served on advisory boards for the following companies: Alpheus Medical, AstraZeneca, Boston Scientific, Carthera, Celularity, GT Medical, Insightec, Lockwood (BlackDiamond), Northwest Biotherapeutics, Novocure, Syneos Health (Boston Biomedical), TriAct Therapeutics, and Varian Medical Systems. RVL is on the scientific advisory board and speakers’ bureau for Merck and on the speakers’ bureau for Novocure; has obtained research support from Bristol-Myers Squibb; and has received honoraria for editing from EBSCO INFORMATION services, Medlink, Neurology, and Elsevier. PK participates in advisory boards for Novocure, Janssen, SDP Oncology, Affinia, Sintetica, Mirati; has done consulting for Biocept, Enclear Therapies, Affinia Therapeutics and Bioclinica; and has received research support from Genentech and Novocure. MC, CD, GB, and AC are employees of Carthera, inventors of patents related to the technology, or have stock ownership in Carthera. AC has received funding support from Horizon 2020 European Innovation Council; is a paid consultant of Carthera; and is part of the Board of Directors of Carthera. JB is vice chair of the Neuro Education Track Subcommittee from the American Society of Anesthesiologists., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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16. Pilot study of repeated blood-brain barrier disruption in patients with mild Alzheimer's disease with an implantable ultrasound device.
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Epelbaum S, Burgos N, Canney M, Matthews D, Houot M, Santin MD, Desseaux C, Bouchoux G, Stroer S, Martin C, Habert MO, Levy M, Bah A, Martin K, Delatour B, Riche M, Dubois B, Belin L, and Carpentier A
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- Blood-Brain Barrier diagnostic imaging, Blood-Brain Barrier metabolism, Brain diagnostic imaging, Brain metabolism, Humans, Neuroimaging methods, Pilot Projects, Positron-Emission Tomography methods, Alzheimer Disease diagnostic imaging, Alzheimer Disease metabolism, Alzheimer Disease therapy, Cognitive Dysfunction metabolism
- Abstract
Background: Temporary disruption of the blood-brain barrier (BBB) using pulsed ultrasound leads to the clearance of both amyloid and tau from the brain, increased neurogenesis, and mitigation of cognitive decline in pre-clinical models of Alzheimer's disease (AD) while also increasing BBB penetration of therapeutic antibodies. The goal of this pilot clinical trial was to investigate the safety and efficacy of this approach in patients with mild AD using an implantable ultrasound device., Methods: An implantable, 1-MHz ultrasound device (SonoCloud-1) was implanted under local anesthesia in the skull (extradural) of 10 mild AD patients to target the left supra-marginal gyrus. Over 3.5 months, seven ultrasound sessions in combination with intravenous infusion of microbubbles were performed twice per month to temporarily disrupt the BBB.
18 F-florbetapir and18 F-fluorodeoxyglucose positron emission tomography (PET) imaging were performed on a combined PET/MRI scanner at inclusion and at 4 and 8 months after the initiation of sonications to monitor the brain metabolism and amyloid levels along with cognitive evaluations. The evolution of cognitive and neuroimaging features was compared to that of a matched sample of control participants taken from the Alzheimer's Disease Neuroimaging Initiative (ADNI)., Results: A total of 63 BBB opening procedures were performed in nine subjects. The procedure was well-tolerated. A non-significant decrease in amyloid accumulation at 4 months of - 6.6% (SD = 7.2%) on18 F-florbetapir PET imaging in the sonicated gray matter targeted by the ultrasound transducer was observed compared to baseline in six subjects that completed treatments and who had evaluable imaging scans. No differences in the longitudinal change in the glucose metabolism were observed compared to the neighboring or contralateral regions or to the change observed in the same region in ADNI participants. No significant effect on cognition evolution was observed in comparison with the ADNI participants as expected due to the small sample size and duration of the trial., Conclusions: These results demonstrate the safety of ultrasound-based BBB disruption and the potential of this technology to be used as a therapy for AD patients. Research of this technique in a larger clinical trial with a device designed to sonicate larger volumes of tissue and in combination with disease-modifying drugs may further enhance the effects observed., Trial Registration: ClinicalTrials.gov, NCT03119961., (© 2022. The Author(s).)- Published
- 2022
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17. Opening of the Blood-Brain Barrier Using Low-Intensity Pulsed Ultrasound Enhances Responses to Immunotherapy in Preclinical Glioma Models.
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Sabbagh A, Beccaria K, Ling X, Marisetty A, Ott M, Caruso H, Barton E, Kong LY, Fang D, Latha K, Zhang DY, Wei J, DeGroot J, Curran MA, Rao G, Hu J, Desseaux C, Bouchoux G, Canney M, Carpentier A, and Heimberger AB
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- Animals, Disease Models, Animal, Mice, Mice, Inbred C57BL, Treatment Outcome, Blood-Brain Barrier radiation effects, Brain Neoplasms therapy, Glioma therapy, Immunotherapy, Ultrasonic Waves
- Abstract
Purpose: The blood-brain barrier (BBB) inhibits adequate dosing/penetration of therapeutic agents to malignancies in the brain. Low-intensity pulsed ultrasound (LIPU) is a safe therapeutic method of temporary BBB disruption (BBBD) to enhance chemotherapeutic delivery to the tumor and surrounding brain parenchyma for treatment of glioblastoma., Experimental Design: We investigated if LIPU could enhance therapeutic efficacy of anti-PD-1 in C57BL/6 mice bearing intracranial GL261 gliomas, epidermal growth factor receptor variant III (EGFRvIII) chimeric antigen receptor (CAR) T cells in NSG mice with EGFRvIII-U87 gliomas, and a genetically engineered antigen-presenting cell (APC)-based therapy producing the T-cell attracting chemokine CXCL10 in the GL261-bearing mice., Results: Mice treated with anti-PD-1 and LIPU-induced BBBD had a median survival duration of 58 days compared with 39 days for mice treated with anti-PD-1, and long-term survivors all remained alive after contralateral hemisphere rechallenge. CAR T-cell administration with LIPU-induced BBBD resulted in significant increases in CAR T-cell delivery to the CNS after 24 ( P < 0.005) and 72 ( P < 0.001) hours and increased median survival by greater than 129%, in comparison with CAR T cells alone. Local deposition of CXCL10-secreting APCs in the glioma microenvironment with LIPU enhanced T-cell glioma infiltration during the therapeutic window ( P = 0.004) and markedly enhanced survival ( P < 0.05)., Conclusions: LIPU increases immune therapeutic delivery to the tumor microenvironment with an associated increase in survival and is an emerging technique for enhancing novel therapies in the brain., (©2021 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2021
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18. Ultrasound-induced blood-brain barrier disruption for the treatment of gliomas and other primary CNS tumors.
- Author
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Beccaria K, Canney M, Bouchoux G, Desseaux C, Grill J, Heimberger AB, and Carpentier A
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- Animals, Humans, Microbubbles, Ultrasonic Waves, Blood-Brain Barrier pathology, Brain Neoplasms therapy, Glioma therapy, Ultrasonic Therapy methods
- Abstract
The treatment of primary brain tumors, especially malignant gliomas, remains challenging. The failure of most treatments for this disease is partially explained by the blood-brain barrier (BBB), which prevents circulating molecules from entering the brain parenchyma. Ultrasound-induced BBB disruption (US-BBBD) has recently emerged as a promising strategy to improve the delivery of therapeutic agents to brain tumors. A large body of preclinical studies has demonstrated that the association of low-intensity pulsed ultrasound with intravenous microbubbles can transiently open the BBB in a localized manner. The safety of this technique has been assessed in numerous preclinical studies in both small and large animal models. A large panel of therapeutic agents have been delivered to the brain in preclinical models, demonstrating both tumor control and increased survival. This technique has recently entered clinical trials with encouraging preliminary data. In this review, we describe the mechanisms and histological effects of US-BBBD and summarize the preclinical studies published to date. We furthermore provide an overview of the current clinical development and future potential of this promising technology., Competing Interests: Declaration of competing interest M. Canney and Guillaume Bouchoux are employees of CarThera. A. Carpentier is a paid consultant to CarThera. K. Beccaria has previously been employed by CarThera. A. Carpentier, K. Beccaria, and M. Canney, and G. Bouchoux are inventors on intellectual property related to the SonoCloud® device that has been licensed to CarThera. A. Carpentier and M. Canney have ownership interest in CarThera., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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19. Ultrasound-mediated Delivery of Paclitaxel for Glioma: A Comparative Study of Distribution, Toxicity, and Efficacy of Albumin-bound Versus Cremophor Formulations.
- Author
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Zhang DY, Dmello C, Chen L, Arrieta VA, Gonzalez-Buendia E, Kane JR, Magnusson LP, Baran A, James CD, Horbinski C, Carpentier A, Desseaux C, Canney M, Muzzio M, Stupp R, and Sonabend AM
- Subjects
- Animals, Blood-Brain Barrier drug effects, Female, Glioma pathology, Male, Mice, Mice, Nude, Microbubbles therapeutic use, Nanoparticles chemistry, Survival Rate, Tissue Distribution, Xenograft Model Antitumor Assays, Albumins pharmacokinetics, Albumins pharmacology, Drug Compounding methods, Drug Delivery Systems methods, Glioma drug therapy, Paclitaxel pharmacokinetics, Paclitaxel pharmacology, Polyethylene Glycols chemistry, Ultrasonography methods
- Abstract
Purpose: Paclitaxel shows little benefit in the treatment of glioma due to poor penetration across the blood-brain barrier (BBB). Low-intensity pulsed ultrasound (LIPU) with microbubble injection transiently disrupts the BBB allowing for improved drug delivery to the brain. We investigated the distribution, toxicity, and efficacy of LIPU delivery of two different formulations of paclitaxel, albumin-bound paclitaxel (ABX) and paclitaxel dissolved in cremophor (CrEL-PTX), in preclinical glioma models., Experimental Design: The efficacy and biodistribution of ABX and CrEL-PTX were compared with and without LIPU delivery. Antiglioma activity was evaluated in nude mice bearing intracranial patient-derived glioma xenografts (PDX). Paclitaxel biodistribution was determined in sonicated and nonsonicated nude mice. Sonications were performed using a 1 MHz LIPU device (SonoCloud), and fluorescein was used to confirm and map BBB disruption. Toxicity of LIPU-delivered paclitaxel was assessed through clinical and histologic examination of treated mice., Results: Despite similar antiglioma activity in vitro , ABX extended survival over CrEL-PTX and untreated control mice with orthotropic PDX. Ultrasound-mediated BBB disruption enhanced paclitaxel brain concentration by 3- to 5-fold for both formulations and further augmented the therapeutic benefit of ABX. Repeated courses of LIPU-delivered CrEL-PTX and CrEL alone were lethal in 42% and 37.5% of mice, respectively, whereas similar delivery of ABX at an equivalent dose was well tolerated., Conclusions: Ultrasound delivery of paclitaxel across the BBB is a feasible and effective treatment for glioma. ABX is the preferred formulation for further investigation in the clinical setting due to its superior brain penetration and tolerability compared with CrEL-PTX., (©2019 American Association for Cancer Research.)
- Published
- 2020
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20. Safety and Feasibility of Repeated and Transient Blood-Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma.
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Idbaih A, Canney M, Belin L, Desseaux C, Vignot A, Bouchoux G, Asquier N, Law-Ye B, Leclercq D, Bissery A, De Rycke Y, Trosch C, Capelle L, Sanson M, Hoang-Xuan K, Dehais C, Houillier C, Laigle-Donadey F, Mathon B, André A, Lafon C, Chapelon JY, Delattre JY, and Carpentier A
- Subjects
- Blood-Brain Barrier, Feasibility Studies, Humans, Magnetic Resonance Imaging, Neoplasm Recurrence, Local, Glioblastoma, Ultrasonic Waves
- Abstract
Purpose: The blood-brain barrier (BBB) limits the efficacy of drug therapies for glioblastoma (GBM). Preclinical data indicate that low-intensity pulsed ultrasound (LIPU) can transiently disrupt the BBB and increase intracerebral drug concentrations., Patients and Methods: A first-in-man, single-arm, single-center trial (NCT02253212) was initiated to investigate the transient disruption of the BBB in patients with recurrent GBM. Patients were implanted with a 1-MHz, 11.5-mm diameter cranial ultrasound device (SonoCloud-1, CarThera). The device was activated monthly to transiently disrupt the BBB before intravenous carboplatin chemotherapy., Results: Between 2014 and 2016, 21 patients were registered for the study and implanted with the SonoCloud-1; 19 patients received at least one sonication. In 65 ultrasound sessions, BBB disruption was visible on T1w MRI for 52 sonications. Treatment-related adverse events observed were transient and manageable: a transient edema at H1 and at D15. No carboplatin-related neurotoxicity was observed. Patients with no or poor BBB disruption ( n = 8) visible on MRI had a median progression-free survival (PFS) of 2.73 months, and a median overall survival (OS) of 8.64 months. Patients with clear BBB disruption ( n = 11) had a median PFS of 4.11 months, and a median OS of 12.94 months., Conclusions: SonoCloud-1 treatments were well tolerated and may increase the effectiveness of systemic drug therapies, such as carboplatin, in the brain without inducing neurotoxicity. See related commentary by Sonabend and Stupp, p. 3750 ., (©2019 American Association for Cancer Research.)
- Published
- 2019
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21. Modeling susceptibility to drug-induced long QT with a panel of subject-specific induced pluripotent stem cells.
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Stillitano F, Hansen J, Kong CW, Karakikes I, Funck-Brentano C, Geng L, Scott S, Reynier S, Wu M, Valogne Y, Desseaux C, Salem JE, Jeziorowska D, Zahr N, Li R, Iyengar R, Hajjar RJ, and Hulot JS
- Subjects
- Anti-Arrhythmia Agents metabolism, Gene Expression Profiling, Humans, Models, Biological, Research Subjects, Arrhythmias, Cardiac chemically induced, Cardiotoxins metabolism, Induced Pluripotent Stem Cells drug effects, Induced Pluripotent Stem Cells physiology, Mass Screening methods
- Abstract
A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes ( DLG2, KCNE4, PTRF, HTR2C , CAMKV ) involved in downstream regulation of cardiac repolarization machinery as underlying high sensitivity to sotalol. Our findings offer novel insights for the development of iPSC-based screening assays for testing individual drug reactions., Competing Interests: SR: Current or former employee of the Cellectis Company. MW: Current or former employee of the Cellectis Company. YV: Current or former employee of the Cellectis Company. CD: Current or former employee of the Cellectis Company. The other authors declare that no competing interests exist.
- Published
- 2017
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22. Targeting herpetic keratitis by gene therapy.
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Elbadawy HM, Gailledrat M, Desseaux C, Ponzin D, and Ferrari S
- Abstract
Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1) can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.
- Published
- 2012
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23. Meganuclease-mediated Inhibition of HSV1 Infection in Cultured Cells.
- Author
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Grosse S, Huot N, Mahiet C, Arnould S, Barradeau S, Clerre DL, Chion-Sotinel I, Jacqmarcq C, Chapellier B, Ergani A, Desseaux C, Cédrone F, Conseiller E, Pâques F, Labetoulle M, and Smith J
- Subjects
- Animals, Blotting, Western, CHO Cells, COS Cells, Cell Line, Chlorocebus aethiops, Cricetinae, Cricetulus, Deoxyribonucleases genetics, Herpesvirus 1, Human genetics, Herpesvirus 1, Human pathogenicity, Humans, Deoxyribonucleases metabolism, Herpesviridae Infections prevention & control
- Abstract
Herpes simplex virus type 1 (HSV1) is a major health problem. As for most viral diseases, current antiviral treatments are based on the inhibition of viral replication once it has already started. As a consequence, they impair neither the viral cycle at its early stages nor the latent form of the virus, and thus cannot be considered as real preventive treatments. Latent HSV1 virus could be addressed by rare cutting endonucleases, such as meganucleases. With the aim of a proof of concept study, we generated several meganucleases recognizing HSV1 sequences, and assessed their antiviral activity in cultured cells. We demonstrate that expression of these proteins in African green monkey kidney fibroblast (COS-7) and BSR cells inhibits infection by HSV1, at low and moderate multiplicities of infection (MOIs), inducing a significant reduction of the viral load. Furthermore, the remaining viral genomes display a high rate of mutation (up to 16%) at the meganuclease cleavage site, consistent with a mechanism of action based on the cleavage of the viral genome. This specific mechanism of action qualifies meganucleases as an alternative class of antiviral agent, with the potential to address replicative as well as latent DNA viral forms.
- Published
- 2011
- Full Text
- View/download PDF
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