Article
Oncology
Francesca Zammarchi, Karin E. G. Havenith, Simon Chivers, Paul Hogg, Francois Bertelli, Peter Tyrer, Narinder Janghra, Halla W. Reinert, John A. Hartley, Patrick H. van Berkel
Summary: ADCT-601 is an antibody-drug conjugate that targets AXL and effectively kills cancer cells by releasing cytotoxin. In preclinical studies, ADCT-601 showed potent antitumor activity and outperformed other drugs in certain situations. It also demonstrated good tolerability and stability.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Christian Werner Wichmann, Ingrid Julienne Georgette Burvenich, Nancy Guo, Angela Rigopoulos, Alexander McDonald, Diana Cao, Graeme Joseph O'Keefe, Sylvia Jie Gong, Hui Kong Gan, Fiona Elizabeth Scott, Nabendu Pore, Steven Coats, Andrew Mark Scott
Summary: This study investigated the biodistribution properties of the anti-ASCT2 antibody drug conjugates (ADCs) MEDI7247 and MEDI7519, as well as an isotype control ADC, using ^89Zr radiolabeling. The results showed that both MEDI7247 and MEDI7519 displayed specific tumor uptake but exhibited faster blood clearance and non-specific localization in the liver. This highlights the importance of nuclear medicine imaging techniques in the early preclinical assessment of drug specificity.
NUCLEAR MEDICINE AND BIOLOGY
(2023)
Article
Chemistry, Applied
Stefan G. Koenig, Remy Angelaud, Christopher M. Crittenden, Kenji Kurita, David J. Russell, Jean-Francois Marcoux, Thomas Matt, Francis Gosselin
Summary: In this study, the synthetic strategies for two distinct but related linker-toxins were reconfigured to establish an efficient and unified supply chain. The streamlined approach avoided challenging desymmetrization efforts and reduced the need for multiple chromatographic purifications, resulting in robust synthetic processes for both compounds 1 and 2.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Oncology
Diana Canals Hernaez, Michael R. Hughes, Yicong Li, Ilaria Mainero Rocca, Pamela Dean, Julyanne Brassard, Erin M. Bell, Ismael Samudio, Anne-Marie Mes-Masson, Yoshiki Narimatsu, Henrik Clausen, Ola Blixt, Calvin D. Roskelley, Kelly M. McNagny
Summary: Podocalyxin is a key cell surface sialomucin that plays a role in tumor metastasis and poor prognosis, with a novel antibody PODO447 showing specificity in targeting tumor cells. PODO447 functions effectively in killing various tumor cell lines and targeting human tumors in xenograft models.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Joshua D. Thomas, Aleksandr Yurkovetskiy, Mao Yin, Natalya D. Bodyak, Dmitry R. Gumerov, Shuyi Tang, Eoin Kelleher, Brian D. Jones, Marina Protopopova, LiuLiang Qin, Alex Uttard, Damon R. Demady, Timothy B. Lowinger
Summary: Pyrrolobenzodiazepine (PBD) polyamide hybrids can serve as effective antibody drug conjugate (ADC) payloads and suppress tumor growth.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Sung Chang Lee, Jennifer S. Y. Ma, Min Soo Kim, Eduardo Laborda, Sei-Hyun Choi, Eric N. Hampton, Hwayoung Yun, Vanessa Nunez, Michelle T. Muldong, Christina N. Wu, Wenxue Ma, Anna A. Kulidjian, Christopher J. Kane, Vadim Klyushnichenko, Ashley K. Woods, Sean B. Joseph, Mike Petrassi, John Wisler, Jing Li, Christina A. M. Jamieson, Peter G. Schultz, Chan Hyuk Kim, Travis S. Young
Summary: The study introduced a unique semisynthetic bispecific antibody, CCW702, which showed specific and potent in vitro cytotoxicity, good tolerability and subcutaneous bioavailability in mice and cynomolgus monkeys, supporting a weekly dosing regimen testing in patients.
Article
Biochemistry & Molecular Biology
Eline A. M. Ruigrok, Nicole S. Verkaik, Erik de Blois, Corrina de Ridder, Debra Stuurman, Stefan J. Roobol, Dik C. Van Gent, Marion de Jong, Wytske M. Van Weerden, Julie Nonnekens
Summary: Combining PSMA-TRT with PARPi did not show synergistic effects on in vitro cell survival or viability in prostate cancer. Only the combination of PSMA-TRT with veliparib resulted in a significant increase in DNA breaks. Furthermore, the combination of PSMA-TRT with PARPi did not improve tumor control compared to PSMA-TRT monotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Yi Zhang, Silvia K. Tacheva-Grigorova, Janette Sutton, Zea Melton, Yvonne S. L. Mak, Cecilia Lay, Bryan A. Smith, Tao Sai, Thomas Van Blarcom, Barbra J. Sasu, Siler H. Panowski
Summary: The purpose of this study was to explore the role of DLL3 in SCLC and evaluate the safety and efficacy of DLL3 CAR T cells. The results showed that DLL3 CAR T cells had a strong anti-tumor effect and no significant tissue damage was observed in the brain and pituitary. Therefore, this study provides a basis for further evaluation of the potential role of DLL3 CAR T cells in the treatment of SCLC.
CLINICAL CANCER RESEARCH
(2023)
Article
Chemistry, Medicinal
Aleksei E. Machulkin, Anastasia A. Uspenskaya, Nikolay Y. Zyk, Ekaterina A. Nimenko, Anton P. Ber, Stanislav A. Petrov, Radik R. Shafikov, Dmitry A. Skvortsov, Galina B. Smirnova, Yulia A. Borisova, Vadim S. Pokrovsky, Vasilii S. Kolmogorov, Alexander N. Vaneev, Yan A. Ivanenkov, Alexander D. Khudyakov, Sergei Kovalev, Alexander S. Erofeev, Petr Gorelkin, Elena K. Beloglazkina, Nikolay Zyk, Elena S. Khazanova, Alexander G. Majouga
Summary: The study focused on developing docetaxel conjugates for prostate cancer treatment, showing promising cytotoxicity and increased solubility compared to the drug itself. In vivo evaluation demonstrated strong inhibitory effects on tumor growth and lower toxicity compared to free docetaxel. The PSMA-targeted docetaxel conjugate is considered a good candidate for further preclinical trials due to its high antitumor activity, reduced side effects, and improved solubility.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Erika Murce, Savanne Beekman, Evelien Spaan, Maryana Handula, Debra Stuurman, Corrina de Ridder, Yann Seimbille
Summary: This study evaluated PSMA-targeting derivatives with modified linker residues and selected the best candidate based on its affinity to PSMA. The lead compound was coupled to a chelator for radiolabeling and subject to dimerization. The resulting molecules, 22 and 30, showed high PSMA specificity and stability when radiolabeled with indium-111. Biodistribution studies in mice models demonstrated that [In-111]In-30 had higher tumor and kidney uptake compared to [In-111]In-PSMA-617, with improved T/K and T/M ratios at 24 h p.i.
Article
Chemistry, Applied
Dane Holte, Meera Rao, Alexander Huters, Justin Simanis, Jean-Christophe Califano, Aaron Kempema, Jean-Noel Levy
Summary: SG3259 is a fully synthetic small molecule with high potency but poor solubility, currently being developed as a warhead for antibody-drug conjugates. The synthesis route is complex and requires a large amount of drug for research and clinical trials.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Oncology
Jamie M. Sperger, Kyle T. Helzer, Charlotte N. Stahlfeld, Dawei Jiang, Anupama Singh, Katherine R. Kaufmann, David J. Niles, Erika Heninger, Nicholas R. Rydzewski, Liguo Wang, Liewei Wang, Rendong Yang, Yanan Ren, Jonathan W. Engle, Peng Huang, Christos E. Kyriakopoulos, Susan F. Slovin, Howard R. Soule, Shuang G. Zhao, Manish Kohli, Scott T. Tagawa, Weibo Cai, Scott M. Dehm, Joshua M. Lang
Summary: This study analyzed the expression of biomarkers in prostate cancer patients and demonstrated that TROP-2 can serve as a cell surface target for isolating circulating tumor cells, and it may serve as a predictive biomarker for antibody-drug conjugates.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Arsyangela Verena, Zhengxing Zhang, Hsiou-Ting Kuo, Helen Merkens, Jutta Zeisler, Ryan Wilson, Shreya Bendre, Antonio A. W. L. Wong, Francois Benard, Kuo-Shyan Lin
Summary: Tumor heterogeneity limits the effectiveness and reliability of monospecific radiopharmaceuticals for prostate cancer diagnosis and therapy. To address this limitation, researchers developed and evaluated three bispecific radiotracers that target both prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are proteins overexpressed in prostate cancer.
Article
Chemistry, Analytical
Florian Fussl, Conor S. Barry, Kathryn M. Pugh, K. Phin Chooi, Balakumar Vijayakrishnan, Gyoung-Dong Kang, Christina von Bulow, Philip W. Howard, Jonathan Bones
Summary: ADCs are a promising class of oncology treatments combining monoclonal antibodies' specificity with small molecule compounds' cytotoxic properties. Monitoring the structure and quality of these toxic molecules is crucial, and SEC-MS method provides a reliable and efficient way to characterize ADCs.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Review
Oncology
Susana Banerjee, Ronny Drapkin, Debra L. Richardson, Michael Birrer
Summary: This article discusses the research progress on NaPi2b as a novel biomarker for treatment and patient selection in ovarian cancer. NaPi2b is highly expressed in ovarian tumors and can be used for tumor mapping and therapeutic targeting. Clinical trial results have shown successful detection of NaPi2b in ovarian cancer patients, and it has the potential to elicit therapeutic responses.
CANCER TREATMENT REVIEWS
(2023)
Article
Hematology
Francesca Zammarchi, Simon Corbett, Lauren Adams, Peter C. Tyrer, Konstantinos Kiakos, Narinder Janghra, Teresa Marafioti, Charles E. Britten, Carin E. G. Havenith, Simon Chivers, Francois D'Hooge, David G. Williams, Arnaud Tiberghien, Philip W. Howard, John A. Hartley, Patrick H. van Berkel
Meeting Abstract
Oncology
Nabendu Pore, M. Jack Borrok, Marlon Rebellato, MaryJane Hinrichs, Kevin P. Schifferli, Noel R. Monks, Ravinder Tammali, Ronald Herbst, Steven R. Coats, David A. Tice
Meeting Abstract
Oncology
Noel R. Monks, Kevin P. Schifferli, Ravinder Tammali, M. Jack Borrok, Steven R. Coats, Ronald Herbst, David A. Tice, Nabendu Pore
Article
Multidisciplinary Sciences
John A. Hartley, Michael J. Flynn, John P. Bingham, Simon Corbett, Halla Reinert, Arnaud Tiberghien, Luke A. Masterson, Dyeison Antonow, Lauren Adams, Sajidah Chowdhury, David G. Williams, Shenlan Mao, Jay Harper, Carin E. G. Havenith, Francesca Zammarchi, Simon Chivers, Patrick H. van Berkel, Philip W. Howard
SCIENTIFIC REPORTS
(2018)
Article
Multidisciplinary Sciences
Matthew J. Sale, Emma Minihane, Noel R. Monks, Rebecca Gilley, Frances M. Richards, Kevin P. Schifferli, Courtney L. Andersen, Emma J. Davies, Mario Aladren Vicente, Eiko Ozono, Aleksandra Markovets, Jonathan R. Dry, Lisa Drew, Vikki Flemington, Theresa Proia, Duncan I. Jodrell, Paul D. Smith, Simon J. Cook
NATURE COMMUNICATIONS
(2019)
Article
Oncology
Simon Corbett, Shiran Huang, Francesca Zammarchi, Philip W. Howard, Patrick H. van Berkel, John A. Hartley
MOLECULAR CANCER THERAPEUTICS
(2020)
Article
Oncology
Francesca Zammarchi, Karin Havenith, Francois Bertelli, Balakumar Vijayakrishnan, Simon Chivers, Patrick H. van Berkel
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Oncology
Francesca Zammarchi, Karin E. G. Havenith, Simon Chivers, Paul Hogg, Francois Bertelli, Peter Tyrer, Narinder Janghra, Halla W. Reinert, John A. Hartley, Patrick H. van Berkel
Summary: ADCT-601 is an antibody-drug conjugate that targets AXL and effectively kills cancer cells by releasing cytotoxin. In preclinical studies, ADCT-601 showed potent antitumor activity and outperformed other drugs in certain situations. It also demonstrated good tolerability and stability.
MOLECULAR CANCER THERAPEUTICS
(2022)
Meeting Abstract
Oncology
Krista Kinneer, Niall J. Dickinson, Luke Masterson, Thais Cailleau, Ian Hutchinson, Balakumar Vijayakrishnan, Nazzareno Dimasi, R. James Christie, Mary McFarlane, Kathryn Ball, Arthur Lewis, Sofia Koch, Lee Brown, Yue Huang, Anton I. Rosenbaum, Jiaqi Yuan, Si Mou, Noel R. Monks, Jon Chesebrough, Ravinder Tammali, Judith Anderton, Darrin Sabol, Frances Anne Tosto, Philipp Wortmann, Zachary A. Cooper, Pauline Ryan, John Hood, Carlos Fernandez Teruel, Carlos Serra Traynor, Andy Pike, Michael Davies, Elisabetta Leo, Kimberly Cook, Nadia Luheshi, Philip W. Howard, Puja Sapra
Meeting Abstract
Clinical Neurology
Robert M. Friedlander, Valentina Di Caro, Diane L. Carlisle, Noel R. Monks, Dani M. Stoltzfus, Natasha L. Bennett, Yalikun Suofu, Jinho Kim, Fang Li, Xiaomin Wang, Stacy M. Yeh, Oxana V. Baranov, Sergei V. Baranov, Barry A. Badeau, Jeremy W. Gleaton, Gabriel A. Cintron-Rosado, Ryan R. Dyer, Dietrich A. Stephan, William R. Mann, Sandra E. Rojas-Caro
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Biotechnology & Applied Microbiology
Noel R. Monks, Renta Hutabarat, Eunah Cho, Barry Badeau, Dani M. Stoltzfus, Anthony Rossomando, William Mann, Dietrich A. Stephan, Sandra Rojas-Caro
Meeting Abstract
Biotechnology & Applied Microbiology
Sandra Rojas-Caro, Renta Hutabarat, Valentina Di Caro, William Riedl, Noel R. Monks, Nathan Tavenor, Barry Badeau, Jeremy Gleaton, Ramesh Batwal, Dani M. Stoltzfus, Anthony Rossomando, William Mann, Dietrich A. Stephan
Article
Immunology
Maria Skaalum Petersen, Marnar Frioheim Kristiansen, Halla Weihe Reinert, Jogvan Pall Fjallsbak, Debes Hammershaimb Christiansen, Shahin Gaini, Bjarni A. Steig, Lars Fodgaard Moller, Marin Strom, Pal Weihe
Summary: Close contacts of COVID-19 patients have a higher risk of SARS-CoV-2 infection, with 5.5% testing positive for total antibody against SARS-CoV-2. Household and young or elderly contacts are at higher risk, with a secondary attack rate of 19.2%. Seroprevalence among close contacts is almost 10 times higher than the general population of the Faroe Islands. Regularly testing these contacts may help in tracking SARS-CoV-2 transmission.
EMERGING INFECTIOUS DISEASES
(2021)
Article
Medicine, Research & Experimental
Kate M. Moore, Ami Desai, Bea de Luxan Delgado, Sara Maria David Trabulo, Claire Reader, Nicholas F. Brown, Elizabeth R. Murray, Adam Brentnall, Philip Howard, Luke Masterson, Francesca Zammarchi, John A. Hartley, Patrick H. van Berkel, John F. Marshall