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36 results on '"Hutchins, Beth"'

7. Phase I Trial of Intravesical Recombinant Adenovirus Mediated Interferon-α2b Formulated in Syn3 for Bacillus Calmette-Guérin Failures in Nonmuscle Invasive Bladder Cancer

Author

Dinney, Colin P.N., Fisher, Mark B., Navai, Neema, OʼDonnell, Michael A., Cutler, David, Abraham, Alice, Young, Sophia, Hutchins, Beth, Caceres, Maria, Kishnani, Narendra, Sode, George, Cullen, Constance, Zhang, Guangcheng, Grossman, Barton H., Kamat, Ashish M., Gonzales, Marshall, Kincaid, Michael, Ainslie, Nancy, Maneval, Daniel C., Wszolek, Matthew F., and Benedict, William F.

Published
2013
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9. Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab

Author

Hutchins, Beth, primary, Starling, Gary C., additional, McCoy, Mark A., additional, Herzyk, Danuta, additional, Poulet, Frederique M., additional, Dulos, John, additional, Liu, Liming, additional, Kang, Soonmo Peter, additional, Fayadat-Dilman, Laurence, additional, Hsieh, Mark, additional, Andrews, Christine L., additional, Ayanoglu, Gulesi, additional, Cullen, Constance, additional, Malefyt, Rene de Waal, additional, Kastelein, Robert A., additional, Saux, Sabine Le, additional, Lee, Julie, additional, Li, Sophie, additional, Malashock, Dan, additional, Sadekova, Svetlana, additional, Soder, George, additional, van Eenennaam, Hans, additional, Willingham, Aarron, additional, Yu, Ying, additional, Streuli, Michel, additional, Carven, Gregory J., additional, and van Elsas, Andrea, additional

Published
2020
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13. Phase I Trial of Intravesical Recombinant Adenovirus-Mediated Interferon-α2b Formulated in Syn3 for BCG failures in Non-Muscle-Invasive Bladder Cancer

Author

Dinney, Colin P.N., Fisher, Mark B., O’Donnell, Michael A., Cutler, David, Abraham, Alice, Young, Sophia, Hutchins, Beth, Caceres, Maria, Kishnani, Narendra, Soder, George, Cullen, Constance, Zhang, Guangcheng, Grossman, H. Barton, Kamat, Ashish M., Gonzales, Marshall, Kincaid, Michael, Ainslie, Nancy, Maneval, Daniel C., Wszolek, Matthew F., Navai, Neema, and Benedict, William F.

Subjects
Adult, Male, Maximum Tolerated Dose, Genetic Vectors, Interferon alpha-2, Disaccharides, Risk Assessment, Article, Drug Administration Schedule, Adenoviridae, Humans, Neoplasm Invasiveness, Treatment Failure, Aged, Aged, 80 and over, Carcinoma, Transitional Cell, Dose-Response Relationship, Drug, Interferon-alpha, Cholic Acids, Genetic Therapy, Middle Aged, Prognosis, Survival Analysis, Recombinant Proteins, Administration, Intravesical, Treatment Outcome, Urinary Bladder Neoplasms, BCG Vaccine, Female, Neoplasm Recurrence, Local
Abstract

A phase I trial of intravesical recombinant adenovirus mediated interferon-α2b gene therapy (rAd-IFNα) formulated with the excipient SCH Syn3 was conducted in patients with nonmuscle invasive bladder cancer who had disease recurrence after treatment with bacillus Calmette-Guérin. The primary objective was to determine the safety of rAd-IFNα/Syn3. Secondary end points were demonstrated effective rAd-IFNα gene expression and preliminary evidence of clinical activity at 3 months.A total of 17 patients with recurrent nonmuscle invasive bladder cancer after bacillus Calmette-Guérin treatment were enrolled in the study. A single treatment of rAd-IFNα (3 × 10(9) to 3 × 10(11) particles per ml) formulated with the excipient Syn3 was administered. Patient safety was evaluated for 12 or more weeks. Efficacy of gene transfer was determined by urine IFNα protein concentrations. Preliminary drug efficacy was determined at 3 months.Intravesical rAd-IFNα/Syn3 was well tolerated as no dose limiting toxicity was encountered. Urgency was the most common adverse event and all cases were grade 1 or 2. rAd-IFNα DNA was not detected in the blood. However, transient low serum IFNα and Syn3 levels were measured. High and prolonged dose related urine IFNα levels were achieved with the initial treatment. Of the 14 patients treated at doses of 10(10) or more particles per ml with detectable urine IFNα, 6 (43%) experienced a complete response at 3 months and 2 remained disease-free at 29.0 and 39.2 months, respectively.Intravesical rAd-IFNα/Syn3 was well tolerated with no dose limiting toxicity encountered. Dose dependent urinary IFNα concentrations confirmed efficient gene transfer and expression. Intravesical rAd-IFNα/Syn3 demonstrated clinical activity in nonmuscle invasive bladder cancer recurring after bacillus Calmette-Guérin.

Published
2013

15. Characterization of Hemodynamic Events Following Intravascular Infusion of Recombinant Adenovirus Reveals Possible Solutions for Mitigating Cardiovascular Responses

Author

Machemer, Todd, primary, Engler, Heidrun, additional, Tsai, Van, additional, Lee, Seoju, additional, Cannon-Carlson, Susan, additional, Voloch, Marcio, additional, Schluep, Thomas, additional, Ravindran, Sundari, additional, Vellekamp, Gary, additional, Brin, Elena, additional, Cornell, Douglas, additional, Sutjipto, Suganto, additional, Wen, Shu Fen, additional, Horn, Mark, additional, Van Rooijen, Nico, additional, Maneval, Dan, additional, Hutchins, Beth, additional, and LaFace, Drake, additional

Published
2005
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20. Adenovirus Reference Materials: Determination of Particle Concentrations Obtained by Orthogonal, Physical-Chemical Methods

Author

Lehmberg, Elisabeth, primary, Shabram, Paul, additional, Schluep, Thomas, additional, Wen, Shu, additional, Hutchins, Beth, additional, Sugarman, Barry, additional, Croyle, Maria, additional, Koehl, Michel, additional, Bonfils, Edwige, additional, Malarme, Daniel, additional, Sharpe, Geoffrey, additional, Nesbit, Heike, additional, Borellini, Flavia, additional, Kamen, Amine, additional, and Vellekamp, Gary, additional

Published
2003
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21. Increased Survival in Sepsis by In Vivo Adenovirus-Induced Expression of IL-10 in Dendritic Cells

Author

Oberholzer, Andreas, primary, Oberholzer, Caroline, additional, Bahjat, Keith S., additional, Ungaro, Ricardo, additional, Tannahill, Cynthia L., additional, Murday, Michelle, additional, Bahjat, Frances R., additional, Abouhamze, Zaher, additional, Tsai, Van, additional, LaFace, Drake, additional, Hutchins, Beth, additional, Moldawer, Lyle L., additional, and Clare-Salzler, Michael J., additional

Published
2002
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23. Adenoviral Delivery of Human and Viral IL-10 in Murine Sepsis

Author

Minter, Rebecca M., primary, Ferry, Maria A., additional, Murday, Michelle E., additional, Tannahill, Cynthia L., additional, Bahjat, Frances R., additional, Oberholzer, Caroline, additional, Oberholzer, Andreas, additional, LaFace, Drake, additional, Hutchins, Beth, additional, Wen, Shufen, additional, Shinoda, Jeremy, additional, Copeland, Edward M., additional, and Moldawer, Lyle L., additional

Published
2001
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25. Extended lung expression and increased tissue localization of viral IL-10 with adenoviral gene therapy

Author

Minter, Rebecca M., primary, Ferry, Maria A., additional, Rectenwald, John E., additional, Bahjat, F. R., additional, Oberholzer, Andreas, additional, Oberholzer, Caroline, additional, La Face, Drake, additional, Tsai, Van, additional, Ahmed, C. M. Iqbal, additional, Hutchins, Beth, additional, Copeland, Edward M., additional, Ginsberg, Harold S., additional, and Moldawer, Lyle L., additional

Published
2000
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26. Working Toward an Adenoviral Vector Testing Standard

Author

Hutchins, Beth, primary, Sajjadi, Nancy, additional, Seaver, Sally, additional, Shepherd, Alasdair, additional, Bauer, Steven R., additional, Simek, Stephanie, additional, Carson, Keith, additional, and Aguilar-Cordova, Estuardo, additional

Published
2000
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31. Influence of recombinant adenovirus on liver injury in endotoxicosis and its modulation by IL-10 expression.

Author

Oberholzer, Caroline, Oberholzer, Andreas, Tschoeke, Sven K., Minter, Rebecca M., Bahjat, Frances R., LaFace, Drake, Hutchins, Beth, and Moldawer, Lyle L.

Abstract

Adenovirus-based gene therapy offers a unique opportunity to target gene expression to the liver by systemic delivery. However, systemic administration of a first generation adenoviral construct elicits an inflammatory response leading to TNF-α-dependent liver injury. The aim of this study was to evaluate whether the systemic administration of recombinant adenovirus exacerbates a subsequent TNF-α-dependent liver injury induced by D-galactosamine and lipopolysaccharide. Surprisingly, low-dose adenovirus administration (105 particles) protects, while high-dose adenovirus (1010 particles) is associated with an exaggerated hepatic inflammatory response from a subsequent D-galactosamine and lipopolysaccharide challenge. This exacerbation is TNF-α dependent, since treatment with a TNF inhibitor fully protects against the liver injury. Moreover, intravenous administration of an adenoviral construct expressing the anti-inflammatory protein interleukin-10 reduces TNF-α appearance and attenuates the increased hepatocyte injury. Taken together, this report demonstrates potential additive effects of TNF-α responses induced by adenovirus and other inflammatory signals, and suggests that the response can be mitigated by relative adenovirus particle dose or by inhibitors, such as TNF-binding protein or interleukin 10. [ABSTRACT FROM PUBLISHER]

Published
2004
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35. Recombinant adenovirus-transduced human dendritic cells engineered to secrete interleukin-10 (IL-10) suppress Th1-type responses while selectively activating IL-10—producing CD4+ T cells

Author

Rea, Delphine, Laface, Drake, Hutchins, Beth, Kwappenberg, Kitty, Melief, Cornelis J.M., Hoeben, Rob C., and Offringa, Rienk

Subjects
*INTERLEUKIN-10, *MAJOR histocompatibility complex, *DENDRITIC cells, *LYMPHOID tissue
Abstract

Abstract: Recombinant adenoviruses (rAd) are efficient tools for genetic modification of human dendritic cells (DC) in vitro. Infection of DCs by rAd encoding β-galactosidase (βgal) results in partial maturation of DCs, as witnessed by the upregulation of major histocompatibility complex and costimulatory molecules. Accordingly, these DCs are more potent stimulators of Th1-type proliferative responses. We now demonstrate that infection of immature DCs with rAd encoding human interleukin (IL)-10 results in the secretion by the DCs of large amounts of IL-10, while not affecting expression of activation markers indicative of partial DC maturation. In contrast to rAd-βgal–infected DCs, rAdIL-10–infected DCs are very poor stimulators of monoclonal and polyclonal Th1-type responses. Instead, stimulation of nonpolarized CD4+ T-cell cultures with rAdIL-10–infected DCs selectively activates and expands an IL-10–producing CD4+ T-cell subset capable of suppressing Th1 responses in vitro. Our data argue that rAd-infected human DCs genetically engineered to produce IL-10 may be exploited for the modulation of harmful Th1-type responses in transplantation and autoimmune diseases. [Copyright &y& Elsevier]

Published
2004
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36. Molnupiravir maintains antiviral activity against SARS-CoV-2 variants and exhibits a high barrier to the development of resistance.

Author

Strizki JM, Gaspar JM, Howe JA, Hutchins B, Mohri H, Nair MS, Kinek KC, McKenna P, Goh SL, and Murgolo N

Subjects
Humans, Antiviral Agents pharmacology, SARS-CoV-2 genetics, COVID-19
Abstract

Molnupiravir, an oral prodrug of N-hydroxycytidine (NHC), previously demonstrated broad in vitro antiviral activity against multiple RNA viruses and has shown a high barrier to the development of resistance. Here, we present the antiviral activity of NHC against recent SARS-CoV-2 variants and the results of resistance selection studies to better understand the potential for viral resistance to NHC. NHC activity against SARS-CoV-2 variants omicron (BA.1, BA.1.1, BA.2, BA.4, BA.4.6, BA.5, BQ.1.1, XBB.1, and XBB.1.5), alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), lambda (C.37), and mu (B.1.621) was evaluated in Vero E6 cells using cytopathic effect assays. Resistance selection studies were performed by passaging SARS-CoV-2 (WA1) in the presence of NHC or a 3C-like protease inhibitor (MRK-A) in Vero E6 cells. Supernatants from cultures exhibiting a cytopathic effect score of ≥2 were re-passaged, and IC 50 values were estimated. Whole-genome deep sequencing was performed on viral RNA isolated at each passage. NHC demonstrated similar potency against all SARS-CoV-2 variants evaluated. No evidence of SARS-CoV-2 phenotypic or genotypic resistance to NHC was observed following 30 passages. A random pattern of nucleotide changes was observed in NHC cultures, consistent with the drug's mechanism of action. In contrast, resistance was readily selected in all three MRK-A control cultures with the selection of a T21I substitution in the 3C-like protease. In conclusion, molnupiravir maintains antiviral activity across all major SARS-CoV-2 variants. Furthermore, no evidence of viral resistance to NHC was observed, supporting previous reports that NHC has a high barrier to developing resistance., Competing Interests: J.S., J.M.G., N.M., J.H., B.H., K.C.K., P.M., and S.L.G. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may own and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA.

Published
2024
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