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53. Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery.

Author

Park, John W, Hong, Keelung, Kirpotin, Dmitri B, Colbern, Gail, Shalaby, Refaat, Baselga, Jose, Shao, Yvonne, Nielsen, Ulrik B, Marks, James D, Moore, Dan, and Papahadjopoulos, Demetrios

Abstract

PURPOSE: Anti-HER2 immunoliposomes combine the tumor-targeting of certain anti-HER2 monoclonal antibodies (MAbs) with the pharmacokinetic and drug delivery capabilities of sterically stabilized liposomes. We previously showed that anti-HER2 immunoliposomes bind efficiently to and internalize in HER2-overexpressing cells in vitro, resulting in intracellular drug delivery.EXPERIMENTAL DESIGN: Here we describe the pharmacokinetics and therapeutic efficacy of anti-HER2 immunoliposomes containing doxorubicin (dox) in a series of animal models.RESULTS: Immunoliposomes displayed long circulation that was identical to that of sterically stabilized liposomes in single- and multiple-dose studies in normal rats. Anti-HER2 immunoliposome-dox produced marked therapeutic results in four different HER2-overexpressing tumor xenograft models, including growth inhibition, regression, and cures. These results demonstrated that encapsulation of dox in anti-HER2 immunoliposomes greatly increased its therapeutic index, both by increasing antitumor efficacy and by reducing systemic toxicity. Immunoliposome-dox was significantly superior to all other treatment conditions tested, including free dox, liposomal dox, and anti-HER2 MAb (trastuzumab). When compared with liposomal dox in eight separate therapy studies in HER2-overexpressing models, immunoliposome delivery produced significantly superior antitumor efficacy in each study (P < 0.0001 to 0.04). Anti-HER2 immunoliposome-dox containing either recombinant human MAb HER2-Fab' or scFv C6.5 yielded comparable therapeutic efficacy. Cure rates for immunoliposome-dox reached 50% (11 of 21) with optimized immunoliposomes and Matrigel-free tumors and overall was 16% (18 of 115) versus no cures (0 of 124) with free dox or liposomal dox. Finally, anti-HER2 immunoliposome-dox was also superior to combinations consisting of free MAb plus free dox or free MAb plus liposomal dox.CONCLUSIONS: Anti-HER2 immunoliposomes produced enhanced antitumor efficacy via targeted delivery.

Published
2002

54. Supplementary Table 4 from MM-141, an IGF-IR– and ErbB3-Directed Bispecific Antibody, Overcomes Network Adaptations That Limit Activity of IGF-IR Inhibitors

Author

Fitzgerald, Jonathan B., primary, Johnson, Bryan W., primary, Baum, Jason, primary, Adams, Sharlene, primary, Iadevaia, Sergio, primary, Tang, Jian, primary, Rimkunas, Victoria, primary, Xu, Lihui, primary, Kohli, Neeraj, primary, Rennard, Rachel, primary, Razlog, Maja, primary, Jiao, Yang, primary, Harms, Brian D., primary, Olivier, Kenneth J., primary, Schoeberl, Birgit, primary, Nielsen, Ulrik B., primary, and Lugovskoy, Alexey A., primary

Published
2023
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55. Supplementary Materials and Methods from MM-141, an IGF-IR– and ErbB3-Directed Bispecific Antibody, Overcomes Network Adaptations That Limit Activity of IGF-IR Inhibitors

Author

Fitzgerald, Jonathan B., primary, Johnson, Bryan W., primary, Baum, Jason, primary, Adams, Sharlene, primary, Iadevaia, Sergio, primary, Tang, Jian, primary, Rimkunas, Victoria, primary, Xu, Lihui, primary, Kohli, Neeraj, primary, Rennard, Rachel, primary, Razlog, Maja, primary, Jiao, Yang, primary, Harms, Brian D., primary, Olivier, Kenneth J., primary, Schoeberl, Birgit, primary, Nielsen, Ulrik B., primary, and Lugovskoy, Alexey A., primary

Published
2023
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56. Supplementary Tables S5, S6, S7, S8 from Enhanced Targeting of the EGFR Network with MM-151, an Oligoclonal Anti-EGFR Antibody Therapeutic

Author

Kearns, Jeffrey D., primary, Bukhalid, Raghida, primary, Sevecka, Mark, primary, Tan, Gege, primary, Gerami-Moayed, Nastaran, primary, Werner, Shannon L., primary, Kohli, Neeraj, primary, Burenkova, Olga, primary, Sloss, Callum M., primary, King, Anne M., primary, Fitzgerald, Jonathan B., primary, Nielsen, Ulrik B., primary, and Wolf, Beni B., primary

Published
2023
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57. Supplementary Figures 1-4, Table 1 from Antitumor Activity of a Novel Bispecific Antibody That Targets the ErbB2/ErbB3 Oncogenic Unit and Inhibits Heregulin-Induced Activation of ErbB3

Author

McDonagh, Charlotte F., primary, Huhalov, Alexandra, primary, Harms, Brian D., primary, Adams, Sharlene, primary, Paragas, Violette, primary, Oyama, Shinji, primary, Zhang, Bo, primary, Luus, Lia, primary, Overland, Ryan, primary, Nguyen, Stephanie, primary, Gu, Jinming, primary, Kohli, Neeraj, primary, Wallace, Matt, primary, Feldhaus, Michael J., primary, Kudla, Arthur J., primary, Schoeberl, Birgit, primary, and Nielsen, Ulrik B., primary

Published
2023
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59. Supplementary Figure Legends from MM-141, an IGF-IR– and ErbB3-Directed Bispecific Antibody, Overcomes Network Adaptations That Limit Activity of IGF-IR Inhibitors

Author

Fitzgerald, Jonathan B., primary, Johnson, Bryan W., primary, Baum, Jason, primary, Adams, Sharlene, primary, Iadevaia, Sergio, primary, Tang, Jian, primary, Rimkunas, Victoria, primary, Xu, Lihui, primary, Kohli, Neeraj, primary, Rennard, Rachel, primary, Razlog, Maja, primary, Jiao, Yang, primary, Harms, Brian D., primary, Olivier, Kenneth J., primary, Schoeberl, Birgit, primary, Nielsen, Ulrik B., primary, and Lugovskoy, Alexey A., primary

Published
2023
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61. Data from MM-141, an IGF-IR– and ErbB3-Directed Bispecific Antibody, Overcomes Network Adaptations That Limit Activity of IGF-IR Inhibitors

Author

Fitzgerald, Jonathan B., primary, Johnson, Bryan W., primary, Baum, Jason, primary, Adams, Sharlene, primary, Iadevaia, Sergio, primary, Tang, Jian, primary, Rimkunas, Victoria, primary, Xu, Lihui, primary, Kohli, Neeraj, primary, Rennard, Rachel, primary, Razlog, Maja, primary, Jiao, Yang, primary, Harms, Brian D., primary, Olivier, Kenneth J., primary, Schoeberl, Birgit, primary, Nielsen, Ulrik B., primary, and Lugovskoy, Alexey A., primary

Published
2023
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62. Supplementary Table S1 from Enhanced Targeting of the EGFR Network with MM-151, an Oligoclonal Anti-EGFR Antibody Therapeutic

Author

Kearns, Jeffrey D., primary, Bukhalid, Raghida, primary, Sevecka, Mark, primary, Tan, Gege, primary, Gerami-Moayed, Nastaran, primary, Werner, Shannon L., primary, Kohli, Neeraj, primary, Burenkova, Olga, primary, Sloss, Callum M., primary, King, Anne M., primary, Fitzgerald, Jonathan B., primary, Nielsen, Ulrik B., primary, and Wolf, Beni B., primary

Published
2023
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65. Supplementary Figures S1-S6 from Cyclophosphamide-Mediated Tumor Priming for Enhanced Delivery and Antitumor Activity of HER2-Targeted Liposomal Doxorubicin (MM-302)

Author

Geretti, Elena, primary, Leonard, Shannon Curtis, primary, Dumont, Nancy, primary, Lee, Helen, primary, Zheng, Jinzi, primary, De Souza, Raquel, primary, Gaddy, Daniel F., primary, Espelin, Christopher W., primary, Jaffray, David A., primary, Moyo, Victor, primary, Nielsen, Ulrik B., primary, Wickham, Thomas J., primary, and Hendriks, Bart S., primary

Published
2023
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69. Supplementary Tables S2, S3, S4 from Enhanced Targeting of the EGFR Network with MM-151, an Oligoclonal Anti-EGFR Antibody Therapeutic

Author

Kearns, Jeffrey D., primary, Bukhalid, Raghida, primary, Sevecka, Mark, primary, Tan, Gege, primary, Gerami-Moayed, Nastaran, primary, Werner, Shannon L., primary, Kohli, Neeraj, primary, Burenkova, Olga, primary, Sloss, Callum M., primary, King, Anne M., primary, Fitzgerald, Jonathan B., primary, Nielsen, Ulrik B., primary, and Wolf, Beni B., primary

Published
2023
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72. Supplementary Figures 1 through 10 and Supplementary Tables 1 through 3 from MM-141, an IGF-IR– and ErbB3-Directed Bispecific Antibody, Overcomes Network Adaptations That Limit Activity of IGF-IR Inhibitors

Author

Fitzgerald, Jonathan B., primary, Johnson, Bryan W., primary, Baum, Jason, primary, Adams, Sharlene, primary, Iadevaia, Sergio, primary, Tang, Jian, primary, Rimkunas, Victoria, primary, Xu, Lihui, primary, Kohli, Neeraj, primary, Rennard, Rachel, primary, Razlog, Maja, primary, Jiao, Yang, primary, Harms, Brian D., primary, Olivier, Kenneth J., primary, Schoeberl, Birgit, primary, Nielsen, Ulrik B., primary, and Lugovskoy, Alexey A., primary

Published
2023
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73. Supplementary Tables S1-S3 from Cyclophosphamide-Mediated Tumor Priming for Enhanced Delivery and Antitumor Activity of HER2-Targeted Liposomal Doxorubicin (MM-302)

Author

Geretti, Elena, primary, Leonard, Shannon Curtis, primary, Dumont, Nancy, primary, Lee, Helen, primary, Zheng, Jinzi, primary, De Souza, Raquel, primary, Gaddy, Daniel F., primary, Espelin, Christopher W., primary, Jaffray, David A., primary, Moyo, Victor, primary, Nielsen, Ulrik B., primary, Wickham, Thomas J., primary, and Hendriks, Bart S., primary

Published
2023
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74. Supplementary Methods, Figures S1-S11, and Table Legends from Enhanced Targeting of the EGFR Network with MM-151, an Oligoclonal Anti-EGFR Antibody Therapeutic

Author

Kearns, Jeffrey D., primary, Bukhalid, Raghida, primary, Sevecka, Mark, primary, Tan, Gege, primary, Gerami-Moayed, Nastaran, primary, Werner, Shannon L., primary, Kohli, Neeraj, primary, Burenkova, Olga, primary, Sloss, Callum M., primary, King, Anne M., primary, Fitzgerald, Jonathan B., primary, Nielsen, Ulrik B., primary, and Wolf, Beni B., primary

Published
2023
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75. Supplementary Materials and Methods from Cyclophosphamide-Mediated Tumor Priming for Enhanced Delivery and Antitumor Activity of HER2-Targeted Liposomal Doxorubicin (MM-302)

Author

Geretti, Elena, primary, Leonard, Shannon Curtis, primary, Dumont, Nancy, primary, Lee, Helen, primary, Zheng, Jinzi, primary, De Souza, Raquel, primary, Gaddy, Daniel F., primary, Espelin, Christopher W., primary, Jaffray, David A., primary, Moyo, Victor, primary, Nielsen, Ulrik B., primary, Wickham, Thomas J., primary, and Hendriks, Bart S., primary

Published
2023
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82. Data from Antitumor Activity of a Novel Bispecific Antibody That Targets the ErbB2/ErbB3 Oncogenic Unit and Inhibits Heregulin-Induced Activation of ErbB3

Author

McDonagh, Charlotte F., primary, Huhalov, Alexandra, primary, Harms, Brian D., primary, Adams, Sharlene, primary, Paragas, Violette, primary, Oyama, Shinji, primary, Zhang, Bo, primary, Luus, Lia, primary, Overland, Ryan, primary, Nguyen, Stephanie, primary, Gu, Jinming, primary, Kohli, Neeraj, primary, Wallace, Matt, primary, Feldhaus, Michael J., primary, Kudla, Arthur J., primary, Schoeberl, Birgit, primary, and Nielsen, Ulrik B., primary

Published
2023
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83. Data from An ErbB3 Antibody, MM-121, Is Active in Cancers with Ligand-Dependent Activation

Author

Schoeberl, Birgit, primary, Faber, Anthony C., primary, Li, Danan, primary, Liang, Mei-Chih, primary, Crosby, Katherine, primary, Onsum, Matthew, primary, Burenkova, Olga, primary, Pace, Emily, primary, Walton, Zandra, primary, Nie, Lin, primary, Fulgham, Aaron, primary, Song, Youngchul, primary, Nielsen, Ulrik B., primary, Engelman, Jeffrey A., primary, and Wong, Kwok-Kin, primary

Published
2023
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84. Supplementary Methods, Figures 1-8, Table 1 from An ErbB3 Antibody, MM-121, Is Active in Cancers with Ligand-Dependent Activation

Author

Schoeberl, Birgit, primary, Faber, Anthony C., primary, Li, Danan, primary, Liang, Mei-Chih, primary, Crosby, Katherine, primary, Onsum, Matthew, primary, Burenkova, Olga, primary, Pace, Emily, primary, Walton, Zandra, primary, Nie, Lin, primary, Fulgham, Aaron, primary, Song, Youngchul, primary, Nielsen, Ulrik B., primary, Engelman, Jeffrey A., primary, and Wong, Kwok-Kin, primary

Published
2023
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87. Estimating waves via measured ship responses

Author

Nielsen, Ulrik D, Bingham, Harry B, Brodtkorb, Astrid H, Iseki, Toshio, Jensen, Jørgen J., Mittendorf, Malte, Mounet, Raphaël E. G., Shao, Yanlin, Storhaug, Gaute, Sørensen, Asgeir J, Takami, Tomoki, Nielsen, Ulrik D, Bingham, Harry B, Brodtkorb, Astrid H, Iseki, Toshio, Jensen, Jørgen J., Mittendorf, Malte, Mounet, Raphaël E. G., Shao, Yanlin, Storhaug, Gaute, Sørensen, Asgeir J, and Takami, Tomoki

Abstract

Optimisation of energy efficiency and operational performance as well as assessment of safety levels and emissions of marine operations require detailed information about the acting wave system. It is possible-with an analogy to classical wave buoys-to estimate the directional wave spectrum by processing sensor measurements of wave-induced responses (e.g., motions and structural responses) from a ship. Compared to other sources of wave data (e.g., buoys, satellites, third-generation wave models), estimation concepts using the ship itself as a buoy provide the wave spectrum at the exact spatio-temporal point, potentially increasing accuracy and with minimal associated cost. This paper gives an overview of the technology, discusses associated uncertainties, and highlights new developments made for estimating waves via measured ship responses.

Published
2023

88. Hull and Propeller Performance Decomposition via an Adaptive Machine Learning Framework

Author

Bertram, Volker, Mittendorf, Malte, Nielsen, Ulrik Dam, Gundermann, Ditte, Bertram, Volker, Mittendorf, Malte, Nielsen, Ulrik Dam, and Gundermann, Ditte

Abstract

This paper deals with a machine learning methodology for decomposing hull and propeller performance. This is facilitated by an ensemble approach predicting both propeller revolutions and shaft power under consistent simulated reference conditions. The derived performance estimates are compared to ISO 19030 and a semi-empirical framework aimed at isolating propeller performance. The case ship is a >300 m cruise vessel sailing in the Caribbean Sea. The auto-logged sensor data covers seven years with three dry-docking intervals and numerous in-water cleaning events. It is concluded that the separation of propeller performance is subject to multiple uncertainty sources and can thus not be reliably assessed. The practical relevance and potential shortcomings of the method are discussed.

Published
2023

89. Nielsen, Ulrik

Author

Nielsen, Ulrik and Nielsen, Ulrik

Published
2023

90. Genetic Variation among Somatic Embryo Clones of Nordmann Fir Grown as Christmas Trees

Author

Xu, Jing, Nielsen, Ulrik Braüner, Xu, Jing, and Nielsen, Ulrik Braüner

Abstract

Somatic embryogenesis (SE) cloning techniques for Nordmann fir Christmas tree production have been pursued and refined in Denmark, and three SE clonal trials with 201 SE clones from seeds of 27 Nordmann fir trees and seedlings from bulk harvest seeds in Georgia, Caucasus, were established from 2014 to 2015. This study was the first to evaluate the genetic performance of these SE clones in different sites. In addition, the performance of SE clones and (zygotic) normal seedlings in the field was compared in this study. This study was based on three key groups of traits for Christmas tree production, measured 5 and 6 years after planting: growth, commercial tree quality, and disorder. Seedlings grew faster and had better Christmas tree quality than SE clones. There were significant family effects for all traits, indicating that a good family also produced good clones on average. Growth and disorder traits were under moderate genetic control, with estimated broad-sense heritability (H-2) from 0.19 to 0.31 and from 0.20 to 0.28, respectively. Quality traits had low to moderate H-2, ranging from 0.09 to 0.24. Significant genotype-by-environment interactions were shown for Christmas tree quality, post-harvest needle retention, and branch angle, suggesting the importance of choosing the right clone at each site. There was no significant interaction in height among the years. Superior clones, compared to the unbred seed source, were identified by combining several important traits. Overall, the somatic clones were well established but had slower growth compared to standard seedlings.

Published
2023

94. Deriving spatial wave data from a network of buoys and ships

Author

Mounet, Raphaël Emile Gilbert, Chen, Jiaxin, Nielsen, Ulrik Dam, Brodtkorb, Astrid H., Pillai, Ajit C., Ashton, Ian G.C., and Steele, Edward C.C.

Subjects
Wave-buoy analogy, Sea state estimation, Machine learning, Metocean conditions, Spectral wave model, Ship motions
Abstract

The real-time provision of high-quality estimates of the ocean wave parameters at appropriate spatial resolutions are essential for the sustainable operations of marine structures. Machine learning affords considerable opportunity for providing additional value from sensor networks, fusing metocean data collected by various platforms. Exploiting the ship-as-a-wave-buoy concept, this article proposes the integration of vessel-based observations into a wave-nowcasting framework. Surrogate models are trained using a high-fidelity physics-based nearshore wave model to learn the spatial correlations between grid points within a computational domain. The performance of these different models are evaluated in a case study to assess how well wave parameters estimated through the spectral analysis of ship motions can perform as inputs to the surrogate system, to replace or complement traditional wave buoy measurements. The benchmark study identifies the advantages and limitations inherent in the methodology incorporating ship-based wave estimates to improve the reliability and availability of regional sea state information.

Published
2023

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