Article
Oncology
Martin Wermke, Enriqueta Felip, Valentina Gambardella, Yasutoshi Kuboki, Daniel Morgensztern, Zohra Oum' Hamed, Meiruo Liu, Matus Studeny, Taofeek K. Owonikoko
Summary: This study aims to investigate the safety and efficacy of the T-cell engager BI 764532 in patients with small-cell lung cancer and other tumors containing DLL3. It also aims to determine the maximum tolerated dose of BI 764532.
Article
Oncology
Michael J. Giffin, Keegan Cooke, Edward K. Lobenhofer, Juan Estrada, Jinghui Zhan, Petra Deegen, Melissa Thomas, Christopher M. Murawsky, Jonathan Werner, Siyuan Liu, Fei Lee, Oliver Homann, Matthias Friedrich, Joshua T. Pearson, Tobias Raum, Yajing Yang, Sean Caenepeel, Jennitte Stevens, Pedro J. Beltran, Jude Canon, Angela Coxon, Julie M. Bailis, Paul E. Hughes
Summary: AMG 757, a bispecific T-cell engager targeting DLL3, demonstrated potent antitumor activity in SCLC models, activating T cells and inducing significant tumor regression. It showed good tolerability in nonhuman primates and has the potential for intermittent administration in patients, suggesting it as a promising option for targeting DLL3-expressing SCLC tumors in clinical settings.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Jonathan Chou, Emily A. Egusa, Sinan Wang, Michelle L. Badura, Fei Lee, Anil P. Bidkar, Jun Zhu, Tanushree Shenoy, Kai Trepka, Troy M. Robinson, Veronica Steri, Jiaoti Huang, Yuzhuo Wang, Eric J. Small, Emily Chan, Bradley A. Stohr, Alan Ashworth, Brant Delafontaine, Sylvie Rottey, Keegan S. Cooke, Nooshin Hashemi Sadraei, Brian Yu, Mark Salvati, Julie M. Bailis, Felix Y. Feng, Robert R. Flavell, Rahul Aggarwal
Summary: The expression of DLL3 in de novo and treatment-emergent small-cell/neuroendocrine (t-SCNC) prostate cancer is associated with reduced survival. A PET agent, [89Zr]-DFO-DLL3-scFv, has been developed to detect DLL3 levels in mouse SCNC models. The DLL3-targeted bispecific T-cell engager (BiTE) immunotherapy, AMG 757 (tarlatamab), exhibits potent and durable antitumor activity in patient-derived xenograft models.
Article
Oncology
Daniel A. Vallera, Felix Oh, Behiye Kodal, Peter Hinderlie, Melissa A. Geller, Jeffrey S. Miller, Martin Felices
Summary: HER2 is a crucial marker in breast cancer therapy, but targeting it in ovarian cancer has shown disappointing results, requiring a more comprehensive approach. A new tri-specific biological drug has been designed to enhance NK cell killing of cancer cells and suppress tumor growth by delivering a natural cytokine signal. The study focuses on a nanobody platform technology that combines targeting and cytokine priming to improve efficacy in ovarian cancer treatment.
Article
Multidisciplinary Sciences
Devivasha Bordoloi, Abhijeet J. Kulkarni, Opeyemi S. Adeniji, M. Betina Pampena, Pratik S. Bhojnagarwala, Shushu Zhao, Candice Ionescu, Alfredo Perales-Puchalt, Elizabeth M. Parzych, Xizhou Zhu, Ali R. Ali, Joel Cassel, Rugang Zhang, Michael R. Betts, Mohamed Abdel-Mohsen, David B. Weiner
Summary: Targeting Siglec-7 antigen can enhance the killing effect of natural killer (NK) cells on ovarian cancer cells and improve treatment outcomes. Additionally, the development of a cell engager that activates NK cells and targets ovarian cancer cells has shown promising results in controlling tumor growth and improving survival rates.
Article
Biology
Ole A. Mandrup, Sui Ching Ong, Simon Lykkemark, Anders Dinesen, Imke Rudnik-Jansen, Niels Frederik Dagnaes-Hansen, Jan Terje Andersen, Luis Alvarez-Vallina, Kenneth A. Howard
Summary: This study introduces a programmable serum half-life extension platform based on human albumin sequences fused with bispecific T-cell engagers, offering potential long-lasting effects, better patient compliance, and the ability to tailor pharmacokinetics to maximize therapeutic efficacy and safety of immuno-oncology targeted biologics.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Michael F. Kaminski, Laura Bendzick, Rachel Hopps, Marissa Kauffman, Behiye Kodal, Yvette Soignier, Peter Hinderlie, Joshua T. Walker, Todd R. Lenvik, Melissa A. Geller, Jeffrey S. Miller, Martin Felices
Summary: This study generated a Tri-specific Killer Engager (TriKE) against TEM8, which selectively activates NK cells to kill TEM8-expressing tumor cells and stromal cells, providing a novel anti-tumor, anti-stroma, and anti-angiogenic cancer therapy for patients with solid tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Multidisciplinary Sciences
Delphine Lissa, Nobuyuki Takahashi, Parth Desai, Irena Manukyan, Christopher W. Schultz, Vinodh Rajapakse, Moises J. Velez, Deborah Mulford, Nitin Roper, Samantha Nichols, Rasa Vilimas, Linda Sciuto, Yuanbin Chen, Udayan Guha, Arun Rajan, Devon Atkinson, Rajaa El Meskini, Zoe Weaver Ohler, Anish Thomas
Summary: This study explores the clinical significance and biological characteristics of neuroendocrine subtypes in small cell lung cancer, as well as the complex variability within and between tumors. NE tumors are more likely to respond to certain treatments but show resistance to chemotherapy, while non-NE tumors may benefit more from immunotherapy.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Lucia Anna Muscarella, Tommaso Mazza, Federico Pio Fabrizio, Angelo Sparaneo, Vito D'Alessandro, Antonio Tancredi, Domenico Trombetta, Flavia Centra, Silvana Pia Muscarella, Concetta Martina Di Micco, Antonio Rossi
Summary: The recent implementation of techniques to study circulating tumor cells has enabled a rapid advancement in understanding the molecular basis of SCLC, revealing its potentially greater heterogeneity and dynamics than previously thought. Despite the lack of established molecular markers for SCLC, neuroendocrine-related transcripts offer promising opportunities in distinguishing and managing different SCLC phenotypes.
Article
Radiology, Nuclear Medicine & Medical Imaging
Frans Suurs, Grit Lorenczewski, Julie M. Bailis, Sabine Stienen, Matthias Friedrich, Fei Lee, Bert van der Vegt, Elisabeth G. E. de Vries, Derk-Jan A. de Groot, Marjolijn N. Lub-de Hooge
Summary: The study developed a fully mouse cross-reactive mesothelin-targeted BiTE molecule with extended half-life, and found that it exhibited specific tumor uptake with higher uptake in lymphoid tissues. The biodistribution and tumor targeting of the molecule varied with different protein doses, with the lowest dose showing similar tumor uptake but faster blood clearance.
JOURNAL OF NUCLEAR MEDICINE
(2021)
Article
Cell Biology
Sudipta Biswas, Kai Kang, Kwok Peng Ng, Tomas Radivoyevitch, Kurt Schalper, Hua Zhang, Daniel J. Lindner, Anish Thomas, David Macpherson, Brian Gastman, David S. Schrump, Kwok-Kin Wong, Vamsidhar Velcheti, Yogen Saunthararajah
Summary: Small cell lung cancers (SCLCs) rapidly develop resistance to chemotherapy and immune checkpoint inhibitor (ICI) treatments. This study found that DNMT1 plays a crucial role in the maturation arrest of SCLC cells. Inhibiting DNMT1/corepressors with clinical compounds extended the survival of mice with chemorefractory and ICI-refractory SCLC.
Article
Toxicology
Tod Harper, Amy Sharma, Sarav Kaliyaperumal, Flordeliza Fajardo, Katie Hsu, Lily Liu, Rhian Davies, Yu-Ling Wei, Jinghui Zhan, Juan Estrada, Majk Kvesic, Lisa Nahrwold, Wibke Deisting, Marc Panzer, Keegan Cooke, Herve Lebrec, Olivier Nolan-Stevaux
Summary: Bispecific T-cell engager (BiTE) molecules have the potential to effectively treat cancer, but their mechanism of action may also cause toxicities in non-tumor tissues. This study investigates the therapeutic potential of an anti-CD70 BiTE molecule (N6P) and demonstrates its ability to kill CD70(+) cancer cells. However, experiments using cynomolgus monkeys reveal adverse inflammation in multiple tissues, indicating the need to understand antigen expression and upregulation to address potential risks associated with off-tumor activity.
TOXICOLOGICAL SCIENCES
(2022)
Article
Oncology
Elisabetta Gambale, Sara Fancelli, Enrico Caliman, Maria Cristina Petrella, Laura Doni, Serena Pillozzi, Lorenzo Antonuzzo
Summary: Cemiplimab, a highly potent monoclonal antibody targeting the PD-1 receptor, has been approved for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma. Recent studies have shown that Cemiplimab improves overall survival, progression free survival, and objective response rate in patients with recurrent/metastatic cervical cancer. It may also provide clinical benefit to patients with penile and vulvar squamous cell carcinoma. However, further research is needed to identify biomarkers for patient selection.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Gastroenterology & Hepatology
Safa Elzein, Fei Bao, Ray Lin, Gabriel Schnickel, Andrew M. Lowy, Gregory P. Botta
Summary: This study reported a case of primary small cell carcinoma of the pancreas treated with a multidisciplinary therapy approach, resulting in an ongoing 28+ month radiographic complete response and overall survival.
BMC GASTROENTEROLOGY
(2021)
Article
Pathology
Minhua Wang, Rita Abi-Raad, Rebecca Baldassarri, Adebowale J. Adeniran, Guoping Cai
Summary: INSM1 is expressed in a significant subset of NSCNELCs, especially in squamous cell carcinomas with basaloid features. Caution should be taken when interpreting INSM1 staining, especially with limited samples. INSM1 should not be solely relied upon as a neuroendocrine marker in distinguishing primary lung tumors.
