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2. Extracellular cold-inducible RNA-binding protein (eCIRP) comme nouveau biomarqueur d’insuffisance rénale aiguë dans un modèle murin d’ischémie-reperfusion rénale, et une cohorte d’arrêts cardiaques

Author

Schleef, M., primary, Baetz, D., additional, Pillot, B., additional, Rabeyrin, M., additional, Bidaux, G., additional, Juillard, L., additional, Guebre-Egziabher, F., additional, Argaud, L., additional, Cour, M., additional, and Lemoine, S., additional

Published
2022
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19. Enhanced CAR T-cell engineering using non-viral Sleeping Beautytransposition from minicircle vectors

Author

Monjezi, R, Miskey, C, Gogishvili, T, Schleef, M, Schmeer, M, Einsele, H, Ivics, Z, and Hudecek, M

Abstract

Immunotherapy with T cell modified with gamma-retroviral or lentiviral (LV) vectors to express a chimeric antigen receptor (CAR) has shown remarkable efficacy in clinical trials. However, the potential for insertional mutagenesis and genotoxicity of viral vectors is a safety concern, and their cost and regulatory demands a roadblock for rapid and broad clinical translation. Here, we demonstrate that CAR T cells can be engineered through non-viral Sleeping Beauty(SB) transposition of CAR genes from minimalistic DNA vectors called minicircles (MCs). We analyzed genomic distribution of SB and LV integrations and show that a significantly higher proportion of MC-derived CAR transposons compared with LV integrants had occurred outside of highly expressed and cancer-related genes into genomic safe harbor loci that are not expected to cause mutagenesis or genotoxicity. CD19-CAR T cells engineered with our enhanced SB approach conferred potent reactivity in vitroand eradicated lymphoma in a xenograft model in vivo. Intriguingly, electroporation of SB MCs is substantially more effective and less toxic compared with conventional plasmids, and enables cost-effective rapid preparation of therapeutic CAR T-cell doses. This approach sets a new standard in advanced cellular and gene therapy and will accelerate and increase the availability of CAR T-cell therapy to treat hematologic malignancies.

Published
2017
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21. Poster Abstracts

Author

Littger, Ralf, primary, Alke, Alexandra, additional, Tewes, Bernhard, additional, Gropp, Felix, additional, Asai, T., additional, Watanabe, K., additional, Kuromi, K., additional, Kurohane, K., additional, Ogino, K., additional, Taki, T., additional, Tsukada, H., additional, Nakayama, J., additional, Oku, N., additional, Babai, I., additional, Matyas, G., additional, Baranji, L., additional, Milosevits, J., additional, Alving, C. R., additional, Bendas, G., additional, Rothe, U., additional, Scherphof, G. L., additional, Kamps, J. A. A. M., additional, Kessner, S., additional, Carafa, M., additional, Di Stefano, A., additional, Sozio, P., additional, Cacciatore, I., additional, Mosciatti, B., additional, Santucci, E., additional, Choice, E., additional, Harvie, P., additional, Galbraith, T., additional, Zunder, E., additional, Dutzar, B., additional, Anklesaria, P., additional, Paul, R., additional, Cocquyt, J., additional, De Cuyper, M., additional, Van der Meeren, P., additional, Cruz, M. E. M., additional, Gaspar, M. M., additional, Silva, M. T., additional, Dathe, M., additional, Nikolenko, H., additional, Wessolowski, A., additional, Schmieder, P., additional, Beyermann, M., additional, Bienert, M., additional, Santos, N. Dos, additional, Cox, K. A., additional, Allen, C., additional, Gallagher, R. C., additional, Ickenstein, L., additional, Mayer, L. D., additional, Bally, M. B., additional, Fischer, S., additional, Margalit, R., additional, Freisleben, H.-J., additional, Garidel, P., additional, Chen, H. C., additional, Moore, D., additional, Mendelsohn, R., additional, Keller, M., additional, Hildebrand, A., additional, Blume, A., additional, Girão da Cruz, M. T., additional, Simões, S., additional, Pedroso de Lima, M. C., additional, Graser, A., additional, Nahde, T., additional, Fahr, A., additional, Müller, R., additional, Müller-Brüsselbach, S., additional, Cudmore, S., additional, O'Mahony, D., additional, Hoving, S., additional, van Tiel, S. T., additional, Seynhaeve, A. L. B., additional, Ambagtsheer, G., additional, Eggermont, A. M. M., additional, ten Hagen, T. L. M., additional, Høyrup, P., additional, Jensen, S. S., additional, Jørgensen, K., additional, Iden, D., additional, Kuang, H., additional, Mullen, P., additional, Jacobs, C., additional, Roben, P., additional, Stevens, T., additional, Lollo, C., additional, Ishida, T., additional, Maeda, R., additional, Masuda, K., additional, Ichihara, M., additional, Kiwada, H., additional, Jung, K., additional, Reszka, R., additional, Kaiser, N., additional, Ohloff, I., additional, Linser-Haar, S., additional, Massing, U., additional, Schubert, R., additional, Kan, P., additional, Tsao, C. W., additional, Chen, W. K., additional, Wang, A. J., additional, Kimpfler, A., additional, Gerber, C., additional, Wieschollek, A., additional, Bruchelt, G., additional, Kobayashi, T., additional, Okada, Y., additional, Sone, S., additional, Harashima, H., additional, Maruyama, K., additional, Kondo, Masayo, additional, Lee, Chun Man, additional, Tanaka, Toshiyuki, additional, Su, Wei, additional, Kitagawa, Toru, additional, Ito, Toshinori, additional, Matsuda, Hikaru, additional, Murai, Toshiyuki, additional, Miyasaka, Masayuki, additional, Junji, Kimura, additional, Kondo, Masami, additional, Asai, Tomohiro, additional, Ogino, Koichi, additional, Taki, Takao, additional, Tsukada, Hideo, additional, Baba, Kazuhiko, additional, Oku, Naoto, additional, Koning, G. A., additional, Wauben, M. H. M., additional, Vestweber, D., additional, Everts, M., additional, Kok, R. J., additional, Schraa, A. J., additional, Molema, G., additional, Schiffelers, R. M., additional, Storm, G., additional, Kristl, J., additional, Šentjurc, M., additional, Abramović, Z., additional, Landry, S., additional, Perron, S., additional, Bestman-Smith, J., additional, Désormeaux, A., additional, Tremblay, M. J., additional, Bergeron, M. G., additional, Madeira, C., additional, Loura, L. M. S., additional, Fedorov, A., additional, Prieto, M., additional, Aires-Barros, M. R., additional, Marques, C. M., additional, Simões, S. I., additional, Cruz, M. E., additional, Cevc, G., additional, Martins, M. B., additional, Moreira, J. N., additional, Gaspar, R., additional, Allen, T. M., additional, Esposito, C., additional, Ortaggi, G., additional, Bianco, A., additional, Bonadies, F., additional, Malizia, D., additional, Napolitano, R., additional, Cametti, C., additional, Mossa, G., additional, Endert, Gerold, additional, Essler, Frank, additional, Lutz, Silke, additional, Panzner, Steffen, additional, Pastorino, F., additional, Brignole, C., additional, Pagnan, G., additional, Moase, E. H., additional, Ponzoni, M., additional, Pavelic, Z., additional, Škalko-Basnet, N., additional, Jalšenjak, I., additional, Penacho, N., additional, Pisano, C., additional, Bucci, F., additional, Serafini, S., additional, Martinelli, R., additional, Cupelli, A., additional, Marconi, A., additional, Ferrara, F. F., additional, Santaniello, M., additional, Critelli, L., additional, Tinti, O., additional, Luisi, P., additional, Carminati, P., additional, Galletti, B., additional, Sauer, I., additional, Schleef, M., additional, Voß, C., additional, Schmidt, T., additional, Flaschel, E., additional, König, S., additional, Wenger, T., additional, Dumond, J., additional, Bogetto, N., additional, Reboud-Ravaux, M., additional, Schramm, H. J., additional, Schramm, W., additional, Sheynis, T., additional, Rozner, S., additional, Kolusheva, S., additional, Satchell, D., additional, Jelnik, R., additional, Shigeta, Y., additional, Imanaka, H., additional, Ando, H., additional, Makino, T., additional, Baba, N., additional, Shimizu, K., additional, Takada, M., additional, Baba, K., additional, Namba, Y., additional, Simberg, Dmitri, additional, Danino, Dganit, additional, Talmon, Yeshayahu, additional, Minsky, Abraham, additional, Ferrari, Marilyn E., additional, Wheeler, Carl J., additional, Barenholz, Yechezkel, additional, Takada, Miki, additional, Shimizu, Kosuke, additional, Kuromi, Koici, additional, Takeuchi, Y., additional, North, J. R., additional, Nango, M., additional, Tewes, B., additional, Köchling, T., additional, Deissler, M., additional, Kühl, C., additional, Marx, U., additional, Strote, G., additional, Gropp, F., additional, Qualls, Marquita M., additional, Kim, Jong-Mok, additional, Thompson, David H., additional, Zhang, Zhi-Yi, additional, Shum, Pochi, additional, Collier, Joel H., additional, Hu, Bi-Huang, additional, Ruberti, Jeffrey W., additional, Messersmith, Phillip B., additional, Tsuruda, T., additional, Nakade, A., additional, Sadzuka, Y., additional, Hirota, S., additional, Sonobe, T., additional, Vorauer-Uhl, K., additional, Wagner, A., additional, Katinger, H., additional, Weeke-Klimp, A. H., additional, Bartsch, M., additional, Meijer, D. K. F., additional, Zeisig, R., additional, Walther, W., additional, Reß, A., additional, Fichtner, I., additional, Zschörnig, O., additional, Schiller, J., additional, Süß, M., additional, Bergmeier, C., additional, Arnold, K., additional, Nchinda, Godwin, additional, Überla, Klaus, additional, and Zschörnig, Olaf, additional

Published
2003
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46. Poster Abstracts

Author

Littger, Ralf, Alke, Alexandra, Tewes, Bernhard, Gropp, Felix, Asai, T., Watanabe, K., Kuromi, K., Kurohane, K., Ogino, K., Taki, T., Tsukada, H., Nakayama, J., Oku, N., Babai, I., Matyas, G., Baranji, L., Milosevits, J., Alving, C. R., Bendas, G., Rothe, U., Scherphof, G. L., Kamps, J. A. A. M., Kessner, S., Rothe, U., Bendas, G., Carafa, M., Di Stefano, A., Sozio, P., Cacciatore, I., Mosciatti, B., Santucci, E., Choice, E., Harvie, P., Galbraith, T., Zunder, E., Dutzar, B., Anklesaria, P., Paul, R., Cocquyt, J., De Cuyper, M., Van der Meeren, P., Cruz, M. E. M., Gaspar, M. M., Silva, M. T., Dathe, M., Nikolenko, H., Wessolowski, A., Schmieder, P., Beyermann, M., Bienert, M., Santos, N. Dos, Cox, K. A., Allen, C., Gallagher, R. C., Ickenstein, L., Mayer, L. D., Bally, M. B., Fischer, S., Margalit, R., Freisleben, H.-J., Garidel, P., Chen, H. C., Moore, D., Mendelsohn, R., Garidel, P., Keller, M., Hildebrand, A., Blume, A., Girão da Cruz, M. T., Simões, S., Pedroso de Lima, M. C., Graser, A., Nahde, T., Fahr, A., Müller, R., Müller-Brüsselbach, S., Harvie, P., Dutzar, B., Choice, E., Cudmore, S., O'Mahony, D., Anklesaria, P., Paul, R., Hoving, S., van Tiel, S. T., Seynhaeve, A. L. B., Ambagtsheer, G., Eggermont, A. M. M., ten Hagen, T. L. M., Høyrup, P., Jensen, S. S., Jørgensen, K., Iden, D., Kuang, H., Mullen, P., Jacobs, C., Roben, P., Stevens, T., Lollo, C., Ishida, T., Maeda, R., Masuda, K., Ichihara, M., Kiwada, H., Jung, K., Reszka, R., Kaiser, N., Ohloff, I., Linser-Haar, S., Massing, U., Schubert, R., Kan, P., Tsao, C. W., Chen, W. K., Wang, A. J., Kimpfler, A., Gerber, C., Wieschollek, A., Bruchelt, G., Schubert, R., Kobayashi, T., Okada, Y., Ishida, T., Sone, S., Harashima, H., Maruyama, K., Kiwada, H., Kondo, Masayo, Lee, Chun Man, Tanaka, Toshiyuki, Su, Wei, Kitagawa, Toru, Ito, Toshinori, Matsuda, Hikaru, Murai, Toshiyuki, Miyasaka, Masayuki, Junji, Kimura, Kondo, Masami, Asai, Tomohiro, Ogino, Koichi, Taki, Takao, Tsukada, Hideo, Baba, Kazuhiko, Oku, Naoto, Koning, G. A., Wauben, M. H. M., ten Hagen, T. L. M., Vestweber, D., Everts, M., Kok, R. J., Schraa, A. J., Molema, G., Schiffelers, R. M., Storm, G., Kristl, J., Šentjurc, M., Abramovi, Z., Landry, S., Perron, S., Bestman-Smith, J., Désormeaux, A., Tremblay, M. J., Bergeron, M. G., Madeira, C., Loura, L. M. S., Fedorov, A., Prieto, M., Aires-Barros, M. R., Marques, C. M., Simões, S. I., Cruz, M. E., Cevc, G., Martins, M. B., Moreira, J. N., Gaspar, R., Allen, T. M., Esposito, C., Ortaggi, G., Bianco, A., Bonadies, F., Malizia, D., Napolitano, R., Cametti, C., Mossa, G., Endert, Gerold, Essler, Frank, Lutz, Silke, Panzner, Steffen, Pastorino, F., Brignole, C., Pagnan, G., Moase, E. H., Allen, T. M., Ponzoni, M., Pavelic, Z., Škalko-Basnet, N., Jalšenjak, I., Penacho, N., Simões, S., Pedroso de Lima, M. C., Pisano, C., Bucci, F., Serafini, S., Martinelli, R., Cupelli, A., Marconi, A., Ferrara, F. F., Santaniello, M., Critelli, L., Tinti, O., Luisi, P., Carminati, P., Santaniello, M., Bucci, F., Tinti, O., Pisano, C., Critelli, L., Galletti, B., Luisi, P., Carminati, P., Sauer, I., Nikolenko, H., Dathe, M., Schleef, M., Voß, C., Schmidt, T., Flaschel, E., König, S., Wenger, T., Dumond, J., Bogetto, N., Reboud-Ravaux, M., Schramm, H. J., Schramm, W., Sheynis, T., Rozner, S., Kolusheva, S., Satchell, D., Jelnik, R., Shigeta, Y., Imanaka, H., Ando, H., Makino, T., Kurohane, K., Oku, N., Baba, N., Shimizu, K., Asai, T., Takada, M., Baba, K., Namba, Y., Oku, N., Simberg, Dmitri, Danino, Dganit, Talmon, Yeshayahu, Minsky, Abraham, Ferrari, Marilyn E., Wheeler, Carl J., Barenholz, Yechezkel, Takada, Miki, Shimizu, Kosuke, Kuromi, Koici, Asai, Tomohiro, Baba, Kazuhiko, Oku, Naoto, Takeuchi, Y., Kurohane, K., North, J. R., Namba, Y., Nango, M., Oku, N., Tewes, B., Köchling, T., Deissler, M., Kühl, C., Marx, U., Strote, G., Gropp, F., Qualls, Marquita M., Kim, Jong-Mok, Thompson, David H., Zhang, Zhi-Yi, Shum, Pochi, Collier, Joel H., Hu, Bi-Huang, Ruberti, Jeffrey W., Messersmith, Phillip B., Thompson, David H., Tsuruda, T., Nakade, A., Sadzuka, Y., Hirota, S., Sonobe, T., Vorauer-Uhl, K., Wagner, A., Katinger, H., Wagner, A., Vorauer-Uhl, K., Katinger, H., Weeke-Klimp, A. H., Bartsch, M., Meijer, D. K. F., Scherphof, G. L., Kamps, J. A. A. M., Zeisig, R., Walther, W., Reß, A., Fichtner, I., Zschörnig, O., Schiller, J., Süß, M., Bergmeier, C., Arnold, K., Nchinda, Godwin, Überla, Klaus, and Zschörnig, Olaf

Abstract

DOCSPER—A Synthetic Lipid Fit for In Vivo ApplicationDOCSPER [1,3-Dioleoyloxy-2-(N5-carbamoyl-spermine)-propane] is a cationic amphiphile consisting of a hydrophobic 1,3 dioleylglycerol moiety and threefold positively charged spermine head group (1). We optimised the 5-step-synthesis of the lipospermine and after up-scaling we have obtained sufficient amounts to initiate preclinical investigations. DOCSPER was tested for its ability to transfect eukaryotic cells in vitro. It has proven to possess high transfection efficiency in comparison to commercially available liposomal transfection agents. Furthermore, DOCSPER was extensively tested in several in vivo studies (23). These studies revealed a high transfection efficiency, whereas very low toxicity levels were detected. Thus, the results clearly indicate that the cationic lipid DOCSPER is a reliable, low-risk system for broad applications in gene therapy.Groth D. et al. Int J Pharm 1998; 162:143–157.Nikol S. et al. Int J Angiol 2000; 9:87–95.Armeanu S. et al. Mol Ther 2000; 1(4):366–375.

Published
1982
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49. In vivo assessment of pediatric kidney function using multi-parametric and multi-nuclear functional magnetic resonance imaging: challenges, perspectives, and clinical applications.

Author

De Mul A, Schleef M, Filler G, McIntyre C, and Lemoine S

Abstract

The conventional methods for assessing kidney function, such as glomerular filtration rate and microalbuminuria, provide only partial insight into kidney function. Multi-parametric and multi-nuclear functional resonance magnetic imaging (MRI) techniques are innovative approaches to unraveling kidney physiology. Multi-parametric MRI includes various sequences to evaluate kidney perfusion, tissue oxygenation, and microstructure characterization, including fibrosis-a key pathological event in acute and chronic kidney disease and in transplant patients-without the need for invasive kidney biopsy. Multi-nuclear MRI detects nuclei other than protons. 23 Na MRI enables visualization of the corticomedullary gradient and assessment of tissue sodium storage, which can be particularly relevant for personalized medicine in salt-wasting tubular disorders. Meanwhile, 31 P-MRS measures intracellular phosphate and ATP variations, providing insights into oxidative metabolism in the muscle during exercise and recovery. This technique can be useful for detecting subclinical ischemia in chronic kidney disease and in tubulopathies with kidney phosphate wasting. These techniques are non-invasive and do not involve radiation exposure, making them especially suitable for longitudinal and serial assessments. They enable in vivo evaluation of kidney function on a whole-organ basis within a short acquisition time and with the ability to distinguish between medullary and cortical compartments. Therefore, they offer considerable potential for pediatric patients. In this review, we provide a brief overview of the main imaging techniques, summarize available literature data on both adult and pediatric populations, and examine the perspectives and challenges associated with multi-parametric and multi-nuclear MRI., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s).)

Published
2024
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50. Telemedical management of symptomatic COVID-19 outpatients.

Author

von Falkenhausen AS, Geipel S, Gail A, Scherer C, Stockhausen S, Sams LE, Becker F, Doldi PM, Lemmermöhle E, de Villèle P, Schleef M, Becker M, Lauterbach M, Massberg S, Kääb S, and Sinner MF

Abstract

Background: COVID-19 remains a challenge to individual health and healthcare resources worldwide. Telemedical surveillance might minimise hospitalisation and direct patient-physician contacts. Yet, randomised clinical trials evaluating telemedical management of COVID-19 patients are lacking., Methods: COVID-SMART is a randomised, open-label, controlled clinical trial investigating whether telemedicine reduces the primary end-point of hospitalisation or any unscheduled utilisation of an emergency medical service within 30 days of follow-up. Key secondary end-points included mortality and primary end-point components. We enrolled acutely infected SARS-CoV-2 patients suitable for outpatient care. All presented with ≥1 risk factor for an adverse COVID-19 course. Patients were randomised 1:1 into a control group receiving standard of care and an intervention group receiving smartphone-based assessment of oxygen saturation, heart rate and electrocardiogram, and telemedical counselling via a 24/7 emergency hotline., Results: Of 607 enrolled patients (mean±sd age 46.7±13.5 years), 304 were randomised into the intervention and 303 into the control group. The primary end-point occurred in 6.9% (n=21) of the intervention and in 9.6% (n=29) of the control group (hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.41-1.26; p=0.24). No deaths occurred during follow-up. Fewer intervention group participants utilised outpatient-based emergency medical services (HR 0.43, 95% CI 0.20-0.90; p=0.03)., Conclusions: COVID-SMART is the first randomised clinical trial assessing the benefit of telemedicine in an acute respiratory infectious disease. Whereas telemedical management did not reduce the primary end-point of hospitalisation, fewer intervention group patients used outpatient-based emergency services, suggesting a potential benefit for less-acutely infected individuals., Competing Interests: Conflict of interest: A.S. von Falkenhausen declares to be granted support from the German Research Foundation. Conflict of interest: C. Scherer reports speaker honoraria from AstraZeneca outside the submitted work. Conflict of interest: P. de Villèle reports being an employee of Withings, the manufacturer of Scanwatch, the smart watch that was used in this trial. Conflict of interest: M.F. Sinner declares being granted support from the German Centre for Cardiovascular Research and with travel support from Biotronik. Conflict of interest: All other authors declare no potential conflict of interest., (Copyright ©The authors 2024.)

Published
2024
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