Editorial Material
Hematology
Tatjana Stankovic, Marwan Kwok
Summary: The study demonstrates the clinical benefit of ibrutinib for relapsed hairy cell leukemia in a phase 2 clinical trial.
Article
Hematology
Kerry A. Rogers, Leslie A. Andritsos, Lai Wei, Eric M. McLaughlin, Amy S. Ruppert, Mirela Anghelina, James S. Blachly, Timothy Call, Dai Chihara, Anees Dauki, Ling Guo, S. Percy Ivy, Lacey R. James, Daniel Jones, Robert J. Kreitman, Gerard Lozanski, David M. Lucas, Apollinaire Ngankeu, Mitch Phelps, Farhad Ravandi, Charles A. Schiffer, William E. Carson, Jeffrey A. Jones, Michael R. Grever
Summary: Ibrutinib may have potential benefits for patients with hairy cell leukemia, especially heavily pretreated patients, with favorable disease control outcomes.
Review
Oncology
Sarah Nocco, Tyler M. Andriano, Arpita Bose, Marina Chilov, Kendra Godwin, George Dranitsaris, Shenhong Wu, Mario E. Lacouture, Lindsay E. Roeker, Anthony R. Mato, Alina Markova
Summary: This study systematically reviewed the incidence and severity of dermatologic toxicities associated with ibrutinib therapy. The analysis revealed that ibrutinib is associated with various dermatologic adverse events, emphasizing the importance for clinicians to be familiar with them for proper management and improved patient outcomes.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Review
Oncology
Andrew H. Lipsky, Nicole Lamanna
Summary: Targeted therapies have revolutionized the frontline treatment for CLL, reducing reliance on chemoimmunotherapy. Drugs such as ibrutinib, acalabrutinib, and venetoclax have shown efficacy in oral therapy. This review explores novel therapeutic strategies using these agents in combination, highlighting the importance of patient characteristics and study methodology.
Article
Oncology
Heidi J. Gray, Payel Chatterjee, Rachele Rosati, Lauren R. Appleyard, Grace J. Durenberger, Robert L. Diaz, Hallie A. Swan, Danielle Peretti, Maddy Pollastro, Trevor Ainge, Katannya Kapeli, Shalini Pereira, Astrid L. Margossian, Kalyan Banda, Barbara A. Goff, Elizabeth M. Swisher, Brady Bernard, Christopher J. Kemp, Carla Grandori
Summary: This article describes a remarkable response to targeted therapy in a patient with platinum-resistant, advanced low-grade serous ovarian cancer. Genomic analysis did not provide obvious therapeutic options, but a drug sensitivity assay identified several potential therapies. This case highlights the clinical utility of ex vivo drug testing of patient-derived tumor organoids as a new approach to identify personalized therapies.
NPJ PRECISION ONCOLOGY
(2023)
Article
Hematology
Aishath Naeem, Filippo Utro, Qing Wang, Justin Cha, Mauno Vihinen, Stephen Martindale, Yinglu Zhou, Yue Ren, Svitlana Tyekucheva, Annette S. Kim, Stacey M. Fernandes, Gordon Saksena, Kahn Rhrissorrakrai, Chaya Levovitz, Brian P. Danysh, Kara Slowik, Raquel A. Jacobs, Matthew S. Davids, James A. Lederer, Rula Zain, C. I. Edvard Smith, Ignaty Leshchiner, Laxmi Parida, Gad Getz, Jennifer R. Brown
Summary: A noncovalent BTK inhibitor called Pirtobrutinib has shown significant clinical activity in patients with chronic lymphocytic leukemia (CLL) whose disease has progressed on covalent BTK inhibitors. It can effectively inhibit BTK-mediated functions and has shown promise in reducing disease progression and improving patient response.
Article
Immunology
Ran Guo, Zhiping Yan, Hanjing Liao, Danfeng Guo, Ruolin Tao, Xiao Yu, Zhixiang Zhu, Wenzhi Guo
Summary: This study found that Ibrutinib can significantly inhibit the activation of neutrophils and macrophages by inhibiting the BTK-PLC gamma 2-PKC signaling pathway, thus playing a therapeutic role in acute inflammatory diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Darshan Joshi, Rajesh Bahekar, Shubhangi Soman, Pradip Jadav, Dipam Patel, Amitgiri Goswami, Jignesh Pethani, Jeevan Kumar, Jitendra Patel, Rajesh Sundar, Poonamgiri Goswami, Krishnarup Goshdastidar, Hoshang Patel, Ankit Patel, Debdutta Bandyopadhyay, Abhijit Chattarjee, Manoranjan Sharma, Mukul Jain, Ranjit Desai
Summary: In this study, novel structural optimizations were conducted to discover effective Bruton's Tyrosine Kinase (BTK) inhibitors for the treatment of autoimmune disorders. Compound 14b was identified as a potent and selective BTK inhibitor with improved oral bioavailability. It displayed strong efficacy in in vitro and in vivo assays, making it a viable therapeutic option for autoimmune disorders.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hui Qiu, Zahid Ali, Andrew Bender, Richard Caldwell, Yi-Ying Chen, Zhizhou Fang, Anna Gardberg, Nina Glaser, Anja Goettsche, Andreas Goutopoulos, Roland Grenningloh, Bettina Hanschke, Jared Head, Theresa Johnson, Christopher Jones, Reinaldo Jones, Shashank Kulkarni, Christine Maurer, Federica Morandi, Constantin Neagu, Sven Poetzsch, Justin Potnick, Ralf Schmidt, Katherine Roe, Ariele Viacava Follis, Carolyn Wing, Xiaohua Zhu, Brian Sherer
Summary: The study unveiled a novel imidazo[4,5-b]pyridine series of potent, selective reversible BTK inhibitors through rational design approach. The lead compound 30 showed 58 nM BTK inhibitory potency in human whole blood and high kinome selectivity, as well as potent dose-dependent efficacy in a rat CIA model. The compound also exhibited favorable pharmacokinetics (PK).
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Manzhi Zhao, Ling Li, Caoimhe H. Kiernan, Melisa D. Castro Eiro, Floris Dammeijer, Marjan van Meurs, Inge Brouwers-Haspels, Merel E. P. Wilmsen, Dwin G. B. Grashof, Harmen J. G. van de Werken, Rudi W. Hendriks, Joachim G. Aerts, Yvonne M. Mueller, Peter D. Katsikis
Summary: Modulating chronic antigen stimulation and T-cell receptor signaling with an ITK inhibitor can reverse ICB resistance in solid tumors and enhance the effectiveness of ICB therapy.
SCIENTIFIC REPORTS
(2023)
Article
Pharmacology & Pharmacy
Fanny Gallais, Loic Ysebaert, Fabien Despas, Sandra De Barros, Lucie Oberic, Ben Allal, Etienne Chatelut, Melanie White-Koning
Summary: This study developed the first PK-PD model for ALC in patients with CLL under ibrutinib treatment. The results of the model suggested that estimated lymphocyte counts in tissues and blood could be used as an early predictor of treatment response in CLL patients.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Tobias Litzenburger, Juergen Steffgen, Ewald Benediktus, Fabian Mueller, Armin Schultz, Elliott Klein, Meera Ramanujam, Christian Harcken, Alpana Gupta, Jing Wu, Sabrina Wiebe, Xiujiang Li, Mary Flack, Steven J. Padula, Sudha Visvanathan, Andreas Huennemeyer, Jianan Hui
Summary: BI 705564 demonstrated good safety, pharmacokinetics, and pharmacodynamics in clinical trials, with efficient target engagement and proof of mechanism shown through effects on allergic skin responses. Mild bleeding-related adverse events were observed, likely due to inhibition of platelet aggregation by BTK inhibition.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Review
Hematology
Alexey V. Danilov, Daniel O. Persky
Summary: Advancements in understanding the disease progression of haematological malignancies have led to the development of novel targeted therapies, such as acalabrutinib, which show promise in improving treatment outcomes for patients with CLL/SLL and MCL. With its high selectivity and potential to reduce off-target toxicity, it has gained accelerated approval for clinical use and has demonstrated efficacy in phase 3 trials.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Oncology
John C. Byrd, Peter Hillmen, Paolo Ghia, Arnon P. Kater, Asher Chanan-Khan, Richard R. Furman, Susan O'Brien, Mustafa Nuri Yenerel, Arpad Illes, Neil Kay, Jose A. Garcia-Marco, Anthony Mato, Javier Pinilla-Ibarz, John F. Seymour, Stephane Lepretre, Stephan Stilgenbauer, Tadeusz Robak, Wayne Rothbaum, Raquel Izumi, Ahmed Hamdy, Priti Patel, Kara Higgins, Sophia Sohoni, Wojciech Jurczak
Summary: In this study, acalabrutinib was found to be noninferior to ibrutinib in terms of progression-free survival in patients with CLL, with a lower incidence of cardiovascular adverse events. This suggests that acalabrutinib may be a more tolerable option for continuous therapy in this patient population.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Review
Chemistry, Medicinal
Fansheng Ran, Yun Liu, Chen Wang, Zhongyuan Xu, Yanan Zhang, Yang Liu, Guisen Zhao, Yong Ling
Summary: Bruton's tyrosine kinase (BTK) plays a crucial role in the treatment of hematologic malignancies, but current therapies have limitations. Therefore, researchers are exploring new treatment strategies, such as next-generation BTK inhibitors, BTK-PROTACs, and combination therapies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Thalia Pacheco-Fernandez, Greta Volpedo, Chaitenya Verma, Abhay R. Satoskar
Summary: Leishmaniasis is a neglected tropical disease transmitted by sand flies and manifests clinically in various forms. Host immune responses are critical in fighting against the disease, but Leishmania parasites manipulate these responses for their own survival. Factors like sand fly salivary proteins and microbiota also influence disease susceptibility.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Cell Biology
N. Fatima, N. Sheikh, A. R. Satoskar, T. Akhtar, A. Tayyeb, I Ashfaq, N. Ryan, S. Ambreen, B. K. Jha, S. Oghumu
Summary: The study revealed that even short-term exposure to tacrolimus (TAC) can induce changes in antioxidant status and lipid peroxidation in the liver of rats, leading to significant alterations in liver structure and increased inflammatory response.
MEDIATORS OF INFLAMMATION
(2021)
Article
Oncology
Kelvin Anderson, Nathan Ryan, Anastasia Alkhimovitch, Arham Siddiqui, Steve Oghumu
Summary: Inhibition of PI3K p110 gamma may enhance the anti-tumor immune response against poorly immunogenic HNSCC, particularly when used in combination with selective checkpoint inhibitors.
Review
Immunology
Thalia Pacheco-Fernandez, Greta Volpedo, Sreenivas Gannavaram, Parna Bhattacharya, Ranadhir Dey, Abhay Satoskar, Greg Matlashewski, Hira L. Nakhasi
Summary: Leishmaniasis is a disease caused by parasitic protozoa transmitted by infected sandflies, affecting over 1 billion people worldwide. The successful vaccination procedure known as leishmanization, which has been used in the Middle East for decades, is no longer practiced due to safety and ethical concerns. New genome editing technologies may allow for the development of a second generation leishmanization that could enter human trials.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Parasitology
Nargis Shaheen, Chaitenya Verma, Thalia Pacheco-Fernandez, Greta Volpedo, Aneeqa Hamid, Ismail Zeb, Syed Aizaz Ali Shah, Shah Fahad, Attiya Iqbal, Asma Ashraf, Amjad Khan, Misbah Gul, Muhammad Ilyas Khan, Huma Fatima, Muhammad Afzal, Abhay R. Satoskar, Naveeda Akhter Qureshi
Summary: This study aimed to elucidate the molecular characterization and genetic diversity of Leishmania spp. in North Eastern Pakistan. The findings confirmed the presence of Leishmania tropica, Leishmania major, and Leishmania infantum, with Leishmania tropica showing significantly higher nucleotide variation. Recommendations for more extensive investigations to understand the molecular epidemiology of Leishmania in the region were made.
Review
Immunology
Greta Volpedo, Ryan H. Huston, Erin A. Holcomb, Thalia Pacheco-Fernandez, Sreenivas Gannavaram, Parna Bhattacharya, Hira L. Nakhasi, Abhay R. Satoskar
Summary: Leishmaniasis is a significant public health issue globally, requiring effective vaccines for prevention and control. The disease leads to long-term disabilities, psycho-sociological trauma, poverty, and gender disparity. Challenges in research include manufacturing vaccines, conducting clinical trials, and defining correlates of protection.
EXPERT REVIEW OF VACCINES
(2021)
Review
Immunology
Greta Volpedo, Thalia Pacheco-Fernandez, Erin A. Holcomb, Natalie Cipriano, Blake Cox, Abhay R. Satoskar
Summary: Leishmaniasis is a neglected tropical disease affecting 12 million people worldwide. Cutaneous leishmaniasis (CL) is the most common form, presenting as ulcerating skin lesions that can self-heal or become chronic. The balance of immune response and inflammatory mediators plays a vital role in the clinical presentation and outcome of the disease.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biology
Subir Karmakar, Nevien Ismail, Fabiano Oliveira, James Oristian, Wen Wei Zhang, Swarnendu Kaviraj, Kamaleshwar P. Singh, Abhishek Mondal, Sushmita Das, Krishna Pandey, Parna Bhattacharya, Greta Volpedo, Sreenivas Gannavaram, Monika Satoskar, Sanika Satoskar, Rajiv M. Sastry, Claudio Meneses, Shinjiro Hamano, Pradeep Das, Greg Matlashewski, Sanjay Singh, Shaden Kamhawi, Ranadhir Dey, Jesus G. Valenzuela, Abhay Satoskar, Hira L. Nakhasi
Summary: Karmakar et al. developed a dermotropic, live attenuated centrin gene-deleted Leishmania major (LmCen(-/-)) vaccine against Visceral Leishmaniasis (VL), demonstrating that a single intradermal injection provides robust and durable protection against lethal VL transmitted through sand fly bites.
COMMUNICATIONS BIOLOGY
(2021)
Review
Immunology
Greta Volpedo, Thalia Pacheco-Fernandez, Parna Bhattacharya, Timur Oljuskin, Ranadhir Dey, Sreenivas Gannavaram, Abhay R. Satoskar, Hira L. Nakhasi
Summary: Leishmaniasis is a disease endemic in tropical and subtropical regions transmitted by infected sand flies. The interactions between Leishmania, host immune cells, and adaptive immunity play a crucial role in disease severity and development. Besides cytokine signals, metabolic shifts in innate cells also influence immune signaling cascades in Leishmania pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Greta Volpedo, Thalia Pacheco-Fernandez, Erin A. Holcomb, Wen-Wei Zhang, Patrick Lypaczewski, Blake Cox, Rebecca Fultz, Chelsea Mishan, Chaitenya Verma, Ryan H. Huston, Abigail R. Wharton, Ranadhir Dey, Subir Karmakar, Steve Oghumu, Shinjiro Hamano, Sreenivas Gannavaram, Hira L. Nakhasi, Greg Matlashewski, Abhay R. Satoskar
Summary: Using the CRISPR/Cas9 technique, researchers have successfully generated live attenuated centrin knockout L. mexicana parasites. These parasites exhibit a growth defect and lower parasitic burdens compared to the wild type, as well as increased production of protective cytokines. In pre-clinical models, immunization with the LmexCen(-/-) parasites is safe and efficacious, leading to protective immunity and reduced parasitic burdens at the infection site and draining lymph nodes.
Review
Microbiology
Greta Volpedo, Parna Bhattacharya, Sreenivas Gannavaram, Thalia Pacheco-Fernandez, Timur Oljuskin, Ranadhir Dey, Abhay R. Satoskar, Hira L. Nakhasi
Summary: Leishmaniasis is a neglected tropical disease that affects millions of people worldwide. Current treatments are not highly effective and have high costs and toxicity. The development of a prophylactic vaccine has become a high priority, but the ability of Leishmania to undermine immune recognition has hindered progress. Live attenuated Leishmania parasites that provide a complete range of antigens could be effective vaccine candidates. This review focuses on the development of live attenuated Leishmania vaccines and discusses the challenges of transitioning from the laboratory to human clinical trials.
Article
Biotechnology & Applied Microbiology
Felipe F. F. Lamenza, Nathan M. M. Ryan, Puja Upadhaya, Arham Siddiqui, Pete P. P. Jordanides, Anna Springer, Peyton Roth, Hasan Pracha, O. Hans Iwenofu, Steve Oghumu
Summary: Head and neck squamous cell carcinoma (HNSCC) is a significant public health problem. We optimized a mouse model of tongue carcinogenesis and found that dietary administration of black raspberries can reduce tumor growth and enhance anti-tumor activity.
CANCER GENE THERAPY
(2023)
Article
Immunology
Nebiye Yentur Doni, Paul J. Bertani, Greta Volpedo, Noushin Saljoughian, Sanjay Varikuti, Greg Matlashewski, Wu Lu, Abhay R. Satoskar
Summary: This article introduces the use of immuno field effect transistors (ImmunoFET) biosensors for monitoring and detecting Leishmania parasites. The current methods of leishmanial diagnosis are time-consuming, costly, and require special equipment and trained personnel. The study demonstrates that ImmunoFET biosensors can successfully detect the presence of Leishmania parasites and have the potential to provide earlier and faster detection of leishmaniasis compared to ELISA.
PARASITE IMMUNOLOGY
(2023)
Article
Oncology
Puja Upadhaya, Nathan Ryan, Peyton Roth, Travis Pero, Felipe Lamenza, Anna Springer, Pete Jordanides, Hasan Pracha, Darrion Mitchell, Steve Oghumu
Summary: This study demonstrates that tumor-targeted radiation therapy can generate tumor antigens that induce strong immune responses. These responses show comparable sensitivity but greater specificity for T cell activation compared to conventional antibodies. This information can be utilized to predict patient responses to radiation and immune therapy.
Meeting Abstract
Public, Environmental & Occupational Health
Subir Karmakar, Nevien Ismail, Wenwei Zhang, Oliveira Fabiano, Greta Volpedo, Shinjiro Hamano, Greg Matlashewski, Shaden Kamhawi, Jesus Valenzuela, Abhay Satoskar, Ranadhir Dey, Hira Nakhasi
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2021)