Article
Pharmacology & Pharmacy
Ophelia Yin, Yuan Xiong, Seiko Endo, Kazutaka Yoshihara, Tushar Garimella, Malaz AbuTarif, Russ Wada, Frank LaCreta
Summary: This study characterized the pharmacokinetics of Trastuzumab deruxtecan in patients with HER2-positive breast cancer or other solid tumor malignancies. Results showed no significant differences in steady-state exposure of the drug in different patient populations, suggesting that dose adjustment based on specific patient characteristics is not necessary.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Ophelia Yin, Hiroji Iwata, Chia-Chi Lin, Kenji Tamura, Junichiro Watanabe, Russ Wada, Helen Kastrissios, Malaz AbuTarif, Tushar Garimella, Caleb Lee, Lin Zhang, Javad Shahidi, Frank LaCreta
Summary: Trastuzumab deruxtecan (T-DXd) has been approved for HER2-positive metastatic breast cancer and gastric cancer, with the 5.4 mg/kg every-3-weeks dosage justified based on exposure-efficacy analysis. Intact T-DXd area under the concentration-time curve was significantly associated with objective response rate, while no significant exposure-response relationships were observed for duration of response or progression-free survival. Higher exposure to T-DXd or released drug was correlated with increased adverse events, suggesting a dose-response relationship with higher ORR and toxicity at 6.4 mg/kg compared to 5.4 mg/kg.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Oncology
Mary Ellen Molloy, Richard J. Austin, Bryan D. Lemon, Wade H. Aaron, Vaishnavi Ganti, Adrie Jones, Susan D. Jones, Kathryn L. Strobel, Purbasa Patnaik, Kenneth Sexton, Laurie Tatalick, Timothy Z. Yu, Patrick A. Baeuerle, Che-Leung Law, Holger Wesche
Summary: HPN536, a trispecific T-cell-activating protein-based construct targeting MSLN-expressing tumor cells, showed potent pharmacologic activity, good tolerability, and extended half-life in nonhuman primates. It is currently undergoing phase I clinical testing for patients with MSLN-expressing malignancies.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Martina S. J. McDermott, Neil A. O'Brien, Benjamin Hoffstrom, KeWei Gong, Ming Lu, Jun Zhang, Tong Luo, Min Liang, Weiping Jia, Jenny J. Hong, Kevin Chau, Simon Davenport, Bin Xie, Michael F. Press, Richard Panayiotou, Abram Handly-Santana, Joan S. Brugge, Leonard Presta, John Glaspy, Dennis J. Slamon
Summary: This study describes the development of a novel antibody-drug conjugate (CLDN6-23-ADC) that selectively targets CLDN6, a potential onco-fetal antigen highly expressed in ovarian and endometrial cancers. The drug exhibits robust tumor regression in mouse models of human ovarian and endometrial cancers and is currently undergoing phase I study.
CLINICAL CANCER RESEARCH
(2023)
Review
Oncology
Brandon M. Bordeau, Joseph P. Balthasar
Summary: The limited efficacy of monoclonal antibody therapies in solid tumors is due to the abnormal vasculature and dense extracellular matrix of tumors, which hinder mAb transport. Strategies to improve mAb uptake in preclinical studies have not yet translated into clinical success.
CANCER BIOLOGY & MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Xiao-yi Zhu, Quan-xiao Li, Yu Kong, Ke-ke Huang, Gang Wang, Yun-ji Wang, Jun Lu, Guo-qiang Hua, Yan-ling Wu, Tian-lei Ying
Summary: Leveraging the specificity of antibody to deliver cytotoxic agent into tumor represents a promising approach in anticancer therapies. This study demonstrated the therapeutic potential of fully human single-domain antibodies (UdAbs) targeting CEACAM5, which effectively inhibited tumor growth in xenograft mice models.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Chemistry, Medicinal
Xinyue Hu, Hailun Jiang, Weiqi Bai, Xiujun Liu, Qingfang Miao, Linlin Wang, Jie Jin, Along Cui, Rui Liu, Zhuorong Li
Summary: ADCs, composed of a monoclonal antibody and warhead, are a successful strategy for treating solid tumors. Novel linker-MMAE conjugates showed increased activity for some ADCs and potential for treating other types of cancer.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Seol Hwa Shin, Yun-Hee Park, Seok Soon Park, Eun Jin Ju, Jin Park, Eun Jeong Ko, Dong Jun Bae, Sang-Yeob Kim, Chul-Woong Chung, Ho Young Song, Se Jin Jang, Seong-Yun Jeong, Si Yeol Song, Eun Kyung Choi
Summary: LCB-ADC exhibits higher cytotoxicity compared to T-DM1 and effectively inhibits tumor growth in animal models with HER2 high expression. Furthermore, LCB-ADC demonstrates good efficacy in suppressing tumor growth in HER2-positive gastric cancer PDX model and T-DM1-resistant models.
Article
Medicine, Research & Experimental
Josefa Dela Cruz Chuh, MaryAnn Go, Yvonne Chen, Jun Guo, Hanine Rafidi, Danielle Mandikian, Yonglian Sun, Zhonghua Lin, Kellen Schneider, Pamela Zhang, Rajesh Vij, Danielle Sharpnack, Pamela Chan, Cecile de la Cruz, Jack Sadowsky, Dhaya Seshasayee, James T. Koerber, Thomas H. Pillow, Gail D. Phillips, Rebecca K. Rowntree, C. Andrew Boswell, Katherine R. Kozak, Andrew G. Polson, Paul Polakis, Shang-Fan Yu, Peter S. Dragovich, Nicholas J. Agard
Summary: Early success with brentuximab vedotin in treating classical Hodgkin lymphoma led to the development of multiple MMAE antibody-drug conjugates, but most of these have not been successful in clinical trials. This study describes the development of second-generation therapeutic ADCs targeting Ly6E, with a focus on using DNA-damaging agents to improve durability of response. The new ADCs showed promising preclinical efficacy in driving tumor regression and reducing the likelihood of resistance compared to traditional MMAE-based conjugates.
Review
Engineering, Multidisciplinary
Ji-Min Dai, Xue-Qin Zhang, Jing-Yao Dai, Xiang-Min Yang, Zhi-Nan Chen
Summary: The modification of therapeutic antibodies is booming in research and development to improve efficacy. China, as an active player in the biopharmaceutical field, shows a great demand and potential in this area.
Article
Oncology
Yutaka Fujiwara, Hirotsugu Kenmotsu, Noboru Yamamoto, Toshio Shimizu, Kan Yonemori, Christopher Ocampo, Apurvasena Parikh, Sumiko Okubo, Kazuteru Fukasawa, Haruyasu Murakami
Summary: Telisotuzumab vedotin demonstrated manageable safety profile and antitumor activity in Japanese patients with advanced solid tumors, with the recommended phase 2 dose confirmed as 2.7 mg/kg every 3 weeks.
Article
Oncology
Yezhe Cheng, Xiaoxi Yuan, Qiang Tian, Xiuying Huang, Yang Chen, Yuzhi Pu, Hu Long, Mingyu Xu, Yafei Ji, Jia Xie, Yuping Tan, Xi Zhao, Hongmei Song
Summary: The study aimed to enhance the intratumoral accumulation of an antibody-drug conjugate (ADC) and reduce its off-target toxicity. SKB264, a novel ADC targeting trophoblast antigen 2 (TROP2), showed promising pharmacologic profiles in vitro and in vivo, with stronger targeting effect and better antitumor activity compared to IMMU-132. These findings suggest the potential therapeutic efficacy of SKB264 for TROP2-positive tumors.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Blair Mcnamara, Michelle Greenman, Nicole Pebley, Levent Mutlu, Alessandro D. Santin
Summary: This review provides an overview of the application of antibody-drug conjugates (ADCs) as a targeted anti-cancer therapy, focusing on the use of HER2-targeting ADC therapy in gynecologic malignancies.
Review
Oncology
Leyin Zhang, Deyi Shen, Lulin Yu, Yici Yan, Harpreet S. Wasan, Jieru Yu, Shuo Zhang, Leitao Sun
Summary: Antibody-drug conjugates (ADCs) have shown promising efficacy and safety in cancer treatment, but their effectiveness for solid tumors requires further investigation.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Article
Medicine, Research & Experimental
Susanne Wingert, Uwe Reusch, Stefan Knackmuss, Michael Kluge, Michael Damrat, Jens Pahl, Ute Schniegler-Mattox, Thomas Mueller, Ivica Fucek, Kristina Ellwanger, Michael Tesar, Torsten Haneke, Joachim Koch, Martin Treder, Wolfgang Fischer, Erich Rajkovic
Summary: The newly developed bispecific antibody AFM24 shows high efficacy against tumor cells expressing varying levels of EGFR, without causing significant toxicity. This antibody demonstrates potent cell killing effects both in vitro and in vivo, indicating its potential as a promising cancer therapy.
Article
Chemistry, Multidisciplinary
Hans-Georg Lerchen, Beatrix Stelte-Ludwig, Sandra Berndt, Anette Sommer, Lisa Dietz, Anne-Sophie Rebstock, Sarah Johannes, Leo Marx, Hannah Joerissen, Christoph Mahlert, Simone Greven
CHEMISTRY-A EUROPEAN JOURNAL
(2019)
Article
Oncology
Sung-Bae Kim, Funda Meric-Bernstam, Aparna Kalyan, Aleksei Babich, Rong Liu, Takahiko Tanigawa, Anette Sommer, Motonobu Osada, Frank Reetz, Dirk Laurent, Sabine Wittemer-Rump, Jordan Berlin
Meeting Abstract
Hematology
Anilkumar Gopalakrishnapillai, Allison Kaeding, Christoph Schatz, Anette Sommer, Soheil Meshinchi, E. Anders Kolb, Sonali Barwe
Article
Chemistry, Medicinal
Julien Lefranc, Volker Klaus Schulze, Roman Christian Hillig, Hans Briem, Florian Prinz, Anne Mengel, Tobias Heinrich, Jozsef Balint, Srinivasan Rengachari, Horst Irlbacher, Detlef Stoeckigt, Ulf Boemer, Benjamin Bader, Stefan Nikolaus Gradl, Carl Friedrich Nising, Franz von Nussbaum, Dominik Mumberg, Daniel Panne, Antje Margret Wengner
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemical Research Methods
Hans-Georg Lerchen, Beatrix Stelte-Ludwig, Anette Sommer, Sandra Berndt, Anne-Sophie Rebstock, Sarah Johannes, Christoph Mahlert, Simone Greven, Lisa Dietz, Hannah Joerissen
BIOCONJUGATE CHEMISTRY
(2020)
Article
Biochemical Research Methods
Renuka Pillutla, Boris Gorovits, Carol Gleason, Jorge Quiroz, David Christopher, Manuela Braun, Catherine Brockus, Douglas Donaldson, Tobias Haslberger, Ling He, Mark Qian, Jens Sydor, Enaksha Wickremsinhe, Lakenya Williams
Article
Oncology
Dennis Kirchhoff, Beatrix Stelte-Ludwig, Hans-Georg Lerchen, Antje Margret Wengner, Oliver von Ahsen, Pascale Buchmann, Stephan Marsch, Christoph Mahlert, Simone Greven, Lisa Dietz, Michael Erkelenz, Ruprecht Zierz, Sandra Johanssen, Dominik Mumberg, Anette Sommer
Article
Oncology
Vincent Chen, Shigeki Umemura, Yumin Han, Renuka Raman, Robin Tucker, Joeffrey Chahine, In-Kyu Kim, Christoph Schatz, Sabine Zitzmann-Kolbe, Anette Sommer, Masanori Onda, Trevor Lee, Yongfeng He, Giuseppe Giaccone
Summary: This study demonstrates that anetumab ravtansine inhibits the growth of MSLN positive thymic carcinoma cells both in vitro and in vivo. The results show that ARav has potential as a novel therapy for thymic carcinoma, especially in cases where traditional therapies have limited effectiveness.
BRITISH JOURNAL OF CANCER
(2022)
Article
Biochemical Research Methods
Anna Lauren, Manuela Braun, Paul Byrne, Chiara Cazzin, Kelly Colletti, Chris Cox, Lisa Dietz, Thomas Emrich, Kristin Geddes, Kate Herr, Tracy Iles, Alexandra Rogue, Yvan Verlinden, Philip Timmerman
Summary: PCR technology is widely used in various laboratory testing fields, with qPCR becoming one of the most well-known laboratory tests globally due to the popularity of COVID-19 infection testing. As translational medicine gains importance in pharmaceutical research and development, PCR and specifically qPCR are becoming standard tools in bioanalytical laboratories.
Article
Oncology
Anette Sommer, Sandra Berndt, Hans-Georg Lerchen, Sabrina Forveille, Allan Sauvat, Dominik Mumberg, Guido Kroemer, Oliver Kepp
Summary: The study characterizes the mode of action of antibody-drug conjugates (ADCs) and finds that they can activate immune responses and induce immunogenic cell death, contributing to their antineoplastic effects.
Editorial Material
Chemistry, Organic
Carl F. Nising, Franz Nussbaum
Summary: This article provides a perspective on the current and future role of synthetic organic chemistry in the Life Science Industry, emphasizing its important enabling role in the revolutionary transformation.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemical Research Methods
Niels Boehnke, Markus Berger, Nils Griebenow, Antje Rottmann, Michael Erkelenz, Stefanie Hammer, Sandra Berndt, Judith Guenther, Antje M. Wengner, Beatrix Stelte-Ludwig, Christoph Mahlert, Simone Greven, Lisa Dietz, Hannah Jorissen, Naomi Barak, Ulf Boemer, Roman C. Hillig, Uwe Eberspaecher, Jorg Weiske, Anja Giese, Dominik Mumberg, Carl Friedrich Nising, Hilmar Weinmann, Anette Sommer
Summary: A new class of NAMPT inhibitors as ADC payloads was developed, optimizing their structures to create highly potent effector chemistries. The optimized NAMPTi-ADCs demonstrated potent in vivo antitumor efficacy with a very good selectivity profile.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Biochemical Research Methods
Anna Lauren, Manuela Braun, Chiara Cazzin, Kelly Colleti, Chris Cox, Lisa Dietz, Thomas Emrich, Kristin Geddes, Kate Herr, Tracy Iles, Alexandra Rogue, Yvan Verlinden, Philip Timmerman
Summary: This manuscript summarizes the discussions of the European Bioanalysis Forum on practical and scientific considerations related to bioanalytical applications of quantitative polymerase chain reaction. It emphasizes the recommendation to consider principles of context of use when defining assay acceptance criteria for method validation criteria and sample analysis.
Review
Medicine, Research & Experimental
Tong-yuan Yang, Manuela Braun, Wibke Lembke, Fraser McBlane, John Kamerud, Stephen DeWall, Edit Tarcsa, Xiaodong Fang, Lena Hofer, Uma Kavita, Vijay V. Upreti, Swati Gupta, LiNa Loo, Alison J. Johnson, Rakesh Kantilal Chandode, Kay-Gunnar Stubenrauch, Maya Vinzing, Cindy Q. Xia, Vibha Jawa
Summary: Immunogenicity poses a challenge to the evaluation of efficacy and safety of AAV gene therapies. Various clinical mitigation strategies have been employed to reduce immunogenicity and achieve desired efficacy, reduce toxicity, or treat more patients who have pre-existing immunity to AAV vectors.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Cell Biology
Richard E. Beatson, Ana C. Parente-Pereira, Leena Halim, Domenico Cozzetto, Caroline Hull, Lynsey M. Whilding, Olivier Martinez, Chelsea A. Taylor, Jana Obajdin, Kim Ngan Luu Hoang, Benjamin Draper, Ayesha Iqbal, Tom Hardiman, Tomasz Zabinski, Francis Man, Rafael T. M. de Rosales, Jinger Xie, Fred Aswad, Daniela Achkova, Chung-Yang Ricardo Joseph, Sara Ciprut, Antonella Adami, Helge G. Roider, Holger Hess-Stumpp, Balazs Gyorffy, Jelmar Quist, Anita Grigoriadis, Anette Sommer, Andrew N. J. Tutt, David M. Davies, John Maher
Summary: Expanding circulating Vγ9Vδ2 T cells in specific culture medium can enhance the therapeutic efficacy and activity of γδT cells in cancer immunotherapy, particularly showing potential treatment activity in leukemia and solid tumor models.
CELL REPORTS MEDICINE
(2021)