Article
Pharmacology & Pharmacy
Ziwei Li, Songren Han, Guilin Cui, Beilin Xue, Jiaxin Li, Yuhong Man, Huan Zhang, Lesheng Teng
Summary: A folic acid-targeted drug delivery system based on liposomes (FA-LP-GCK) was developed to treat rheumatoid arthritis (RA). The FA-LP-GCK showed high stability, encapsulation efficiency, and demonstrated strong anti-inflammatory and therapeutic effects in both cell and animal experiments.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Diana Guimaraes, Franck Lager, Gilles Renault, Jamil Guezguez, Michael Burnet, Joana Cunha, Artur Cavaco-Paulo, Eugenia Nogueira
Summary: Methotrexate (MTX) is commonly used as a first-line therapy for rheumatoid arthritis (RA), but its side effects can limit its use. Folate-targeted liposomal formulation of MTX (FL-MTX) is a modified nanotherapeutic treatment that has shown good therapeutic efficacy in a mouse model of collagen-induced arthritis (CIA). FL-MTX can reduce the hepatic and renal elimination of MTX, leading to a potential reduction in treatment frequency and overall dosage.
Article
Immunology
Junnan Zhou, Yuhang Mao, Xiaotian Shi, Yudie Zhang, Xiaolu Yu, Xuan Liu, Li Diao, Xue Yang, Changze Liu, Dan Liu, Xin Tan, Mei Liu
Summary: This study demonstrates the potential therapeutic effect of peimine on rheumatoid arthritis (RA), including the inhibition of destructive behaviors and over-expression of pro-inflammatory cytokines. It also provides insights into the molecular mechanism of action of peimine on RA.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Gang Chen, Yuhang Mao, Jing Wang, Junnan Zhou, Li Diao, Sirui Wang, Wenjuan Zhao, Xinyi Zhu, Xiaolu Yu, Fuli Zhao, Xuan Liu, Mei Liu
Summary: Phillyrin shows potential as a therapeutic agent for rheumatoid arthritis by inhibiting inflammatory cell activity and reducing symptoms of arthritis and bone erosion.
ARABIAN JOURNAL OF CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Donghao Gan, Wenxiang Cheng, Liqing Ke, Antonia RuJia Sun, Qingyun Jia, Jianhai Chen, Jietao Lin, Jian Li, Zhanwang Xu, Peng Zhang
Summary: Clinical studies have shown that pirfenidone effectively relieves joint pain in rheumatoid arthritis patients. This study investigated the repurposing of pirfenidone for RA treatment and explored its anti-rheumatic mechanisms. Through in vivo and in vitro models, the study suggested that pirfenidone may alleviate pathological changes in RA by inhibiting inflammation and angiogenesis through multiple pathways such as JAK2/STAT3 and Akt.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Zihan Xu, Wei Shang, Zhiming Zhao, Beibei Zhang, Chunli Liu, Hui Cai
Summary: This study found that curcumin can improve rheumatoid arthritis by inhibiting cell proliferation, migration, invasion, and promoting cell apoptosis. Curcumin also reduces inflammation by decreasing the secretion of inflammatory factors. Therefore, curcumin may be a promising candidate for treating RA.
Article
Nutrition & Dietetics
Jisu Park, Ji Hyeon Ryu, Bo-Young Kim, Hyun Soo Chun, Min Sun Kim, Yong-Il Shin
Summary: Fermented lettuce extract (FLE) has therapeutic effects on collagen-induced arthritis (CIA) and rheumatoid arthritis (RA) by suppressing inflammation and cartilage degradation. FLE inhibits the TGF-beta/Smad signaling pathway and induces autophagy in MH7A cells.
Article
Cell Biology
Shih-Yao Chen, Jeng-Long Hsieh, Po-Ting Wu, Ai-Li Shiau, Chao-Liang Wu
Summary: This study found that decreased expression of miR-133 is associated with aberrant proliferation and migration of RA FLS. Overexpression of miR-133 reduced cell viability and migration of RA FLS, with decreased levels of FSCN1, EGFR, and MET.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Xin Ba, Ying Huang, Pan Shen, Yao Huang, Hui Wang, Liang Han, Wei Ji Lin, Hui Jia Yan, Li Jun Xu, Kai Qin, Zhe Chen, Sheng Hao Tu
Summary: Wutou Decoction (WTD) has shown to ameliorate symptoms and synovial pannus hyperplasia in collagen-induced arthritis (CIA) rats, inhibit proliferation, migration and invasion of MH7A cells, induce apoptosis, and block proangiogenic factors. The potential mechanism of WTD in inhibiting angiogenesis in rheumatoid arthritis (RA) is likely through the PI3K-AKT-mTOR-HIF-1 alpha pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xiaolu Yu, Junnan Zhou, Fuli Zhao, Xuan Liu, Yuhang Mao, Li Diao, Chuanjun Wen, Mei Liu
Summary: Tomatidine (Td) shows inhibitory effects on inflammatory responses in arthritis and therapeutic effects on synovial inflammation and joint destruction in rats. Td can significantly suppress the production of pro-inflammatory cytokines and may act by reducing the activation of MAPKs and NF-κB.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Xiao-feng Li, Shu-qin Yin, Hao Li, Ying-li Yang, Xin Chen, Biao Song, Sha Wu, Yuan-yuan Wu, Hua Wang, Jun Li
Summary: This study found that reduced expression of PPAR-gamma and increased expression of TNF-alpha are important factors in the inflammatory response of synoviocytes in rheumatoid arthritis. By binding with p53, PPAR-gamma can alleviate the activation and inflammation of synoviocytes induced by TNF-alpha.
ACTA PHARMACOLOGICA SINICA
(2023)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Edgar Zamora, Ana Y. Valdivia, Arun Kumar, Kwang J. Chun
Summary: Spinal facet joint septic arthritis is a rare pathology associated with pyogenic organisms, presenting with symptoms such as back pain, fever, and positive bacterial blood cultures. Diagnosis relies on MRI imaging, which is unable to differentiate the condition from other inflammatory arthropathies.
CLINICAL NUCLEAR MEDICINE
(2021)
Article
Integrative & Complementary Medicine
Wei-Jen Cheng, Hsuan-Tzu Yang, Chih-Chao Chiang, Kuei-Hung Lai, Yu-Li Chen, Huei-Lin Shih, Jong-Jen Kuo, Tsong-Long Hwang, Chi-Chien Lin
Summary: This study investigates the anti-arthritic and anti-inflammatory effects of deer velvet antler (DA) on rheumatoid arthritis (RA). The results show that DA can reduce inflammation and alleviate arthritis symptoms and tissue damage in experimental models. Additionally, several components potentially related to the anti-inflammatory effects of DA were identified.
AMERICAN JOURNAL OF CHINESE MEDICINE
(2022)
Article
Rheumatology
Meilang Xue, Haiyan Lin, Hai Po Helena Liang, Kelly McKelvey, Ruilong Zhao, Lyn March, Christopher Jackson
Summary: The study found that deficiency of PAR1 or PAR2 exacerbates inflammatory arthritis in CIA. The protective functions of PAR1 and PAR2 in CIA likely occur via differing mechanisms involving immune cell differentiation and cytokines/MMPs.
Article
Immunology
Yan Zhao, Xialin Sun, Jun Lin, Tingwen Zhang, Shuangli Liu, Zhaowei Yan
Summary: Panaxynol (PAL) can promote apoptosis and inhibit proliferation, migration, and invasion of fibroblast-like synovial cells in rheumatoid arthritis (RA). PAL can also reduce joint swelling and inflammatory infiltration in CIA rats, mainly through the TLR4/NF-kappa B signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Enrique J. Arenas, Alex Martinez-Sabadell, Irene Rius Ruiz, Macarena Roman Alonso, Marta Escorihuela, Antonio Luque, Carlos Alberto Fajardo, Alena Gros, Christian Klein, Joaquin Arribas
Summary: Immunotherapy has shown promise in cancer treatment, with T cell bispecific antibodies (TCBs) and chimeric antigen receptors (CARs) being potential tools for this approach. This study reveals that disruption of interferon-gamma signaling, including downregulation of JAK2, in cancer cells confers resistance to T cell-mediated cytotoxicity directed against HER2, highlighting a potential mechanism for resistance to T cell-engaging therapies.
NATURE COMMUNICATIONS
(2021)
Correction
Oncology
Johannes Sam, Sara Colombetti, Tanja Fauti, Andreas Roller, Marlene Biehl, Linda Fahrni, Valeria Nicolini, Mario Perro, Tapan Nayak, Esther Bommer, Anne Schoenle, Maria Karagianni, Marine Le Clech, Nathalie Steinhoff, Christian Klein, Pablo Umana, Marina Bacac
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Pablo Moreno-Ruiz, Sara Corvigno, Nienke C. te Grootenhuis, Linnea La Fleur, Max Backman, Carina Strell, Artur Mezheyeuski, Gabriele Hoelzlwimmer, Christian Klein, Johan Botling, Patrick Micke, Arne Ostman
Summary: This study identifies high stromal FAP expression as a poor prognostic marker for survival in NSCLC patients, particularly in adenocarcinoma patients. Additionally, it reveals associations between α-SMA and FAP expression with specific clinical characteristics like p53 mutations and CD8 infiltration levels.
Article
Hematology
Christian Augsberger, Gerulf Hanel, Wei Xu, Vesna Pulko, Lydia Jasmin Hanisch, Angelique Augustin, John Challier, Katharina Hunt, Binje Vick, Pier Eduardo Rovatti, Christina Krupka, Maurine Rothe, Anne Schonle, Johannes Sam, Emmanuelle Lezan, Axel Ducret, Daniela Ortiz-Franyuti, Antje-Christine Walz, Jorg Benz, Alexander Bujotzek, Felix S. Lichtenegger, Christian Gassner, Alejandro Carpy, Victor Lyamichev, Jigar Patel, Nikola Konstandin, Antje Tunger, Marc Schmitz, Michael Von Bergwelt-Baildon, Karsten Spiekermann, Luca Vago, Irmela Jeremias, Estelle Marrer-Berger, Pablo Umana, Christian Klein, Marion Subklewe
Summary: The novel T-cell bispecific (TCB) antibody targets intracellular antigens, recognizing multiple leukemia-associated targets. WT1-TCB demonstrates potent killing of AML cells through various methods, with enhanced cytotoxicity when combined with immunomodulatory drugs.
Article
Immunology
Vittoria Massafra, Sofia Tundo, Aline Dietzig, Axel Ducret, Christian Jost, Christian Klein, Roland E. Kontermann, Hendrik Knoetgen, Martin Steegmaier, Andrea Romagnani, Yvonne A. Nagel
Summary: This study explores the potential of targeted protein degradation in tumor cells to enhance T cell effector function, and for the first time investigates the impact of combining a degrader and a TCB in cancer immunotherapy.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Biology
S. Jordan Kerns, Chaitra Belgur, Debora Petropolis, Marianne Kanellias, Riccardo Barrile, Johannes Sam, Tina Weinzierl, Tanja Fauti, Anne Freimoser-Grundschober, Jan Eckmann, Carina Hage, Martina Geiger, Patrick Ray Ng, William Tien-Street, Dimitris Manatakis, Virginie Micallef, Regine Gerard, Michael Bscheider, Ekaterina Breous-Nystrom, Anneliese Schneider, Anna Maria Giusti, Cristina Bertinetti-Lapatki, Heather Shannon Grant, Adrian B. Roth, Geraldine A. Hamilton, Thomas Singer, Katia Karalis, Annie Moisan, Peter Bruenker, Christian Klein, Marina Bacac, Nikolce Gjorevski, Lauriane Cabon
Summary: This study demonstrated the unprecedented capability of two human Organs-on-Chips in evaluating the safety profile of T-cell bispecific antibodies targeting tumor antigens, predicting TCB safety liabilities based on target expression and antibody affinity. These novel tools broaden research options for understanding engineered therapeutic antibodies and assessing safety in tissues susceptible to adverse events.
Article
Biochemistry & Molecular Biology
Steffen Dickopf, Can Buldun, Vedran Vasic, Guy Georges, Carina Hage, Klaus Mayer, Matthias Forster, Uwe Wessels, Kay-Gunnar Stubenrauch, Jorg Benz, Andreas Ehler, Matthias E. Lauer, Philippe Ringler, Sebastian Kobold, Stefan Endres, Christian Klein, Ulrich Brinkmann
Summary: The field of multi-specific antibody derivatives is rapidly growing, with domain exchange reactions being able to generate hybrid antibodies under physiological conditions for potential therapeutic applications.
BIOLOGICAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Alvaro Teijeira, Itziar Migueliz, Saray Garasa, Vaios Karanikas, Carlos Luri, Asunta Cirella, Irene Olivera, Marta Canamero, Maite Alvarez, Maria C. Ochoa, Ana Rouzaut, Maria E. Rodriguez-Ruiz, Miguel F. Sanmamed, Christian Klein, Pablo Umana, Mariano Ponz, Marina Bacac, Ignacio Melero
Summary: In this study, the performance of the CEA-CD3 T cell bispecific antibody cibisatamab in three-dimensional tumor organoids cocultured with T cells was investigated using time-lapse confocal microscopy. The results showed that the killing of tumor cells was dependent on the levels of surface CEA expression, and the higher affinity CEACAM5-CD3 bispecific antibody remained active on low CEA expressing organoids. Additionally, the coculture of tumor organoids, autologous fibroblasts, and T cells demonstrated a costimulatory effect of anti-FAP-4-1BBL antibody, leading to enhanced tumor cell killing.
Article
Oncology
Gabrielle Leclercq, Llucia Alberti Servera, Sabrina Danilin, John Challier, Nathalie Steinhoff, Claudia Bossen, Alex Odermatt, Valeria Nicolini, Pablo Umana, Christian Klein, Marina Bacac, Anna-Maria Giusti, Anneliese Schneider, Helene Haegel
Summary: This study investigated the biological mechanisms of cytokine release after treatment with T cell bispecific antibodies (TCBs) and identified T cells as the triggers and monocytes and neutrophils as the amplifiers of the cytokine cascade. Moreover, it demonstrated the contribution of neutrophils to TCB-mediated cytokine release using single-cell RNA sequencing.
Article
Oncology
Gabrielle Leclercq, Helene Haegel, Alberto Toso, Tina Zimmermann, Luke Green, Nathalie Steinhoff, Johannes Sam, Vesna Pulko, Anneliese Schneider, Anna Maria Giusti, John Challier, Anne Freimoser-Grundschober, Laurent Lariviere, Alex Odermatt, Martin Stern, Pablo Umana, Marina Bacac, Christian Klein
Summary: This study aimed to identify small molecules that can reduce cytokine release while maintaining T cell-mediated tumor killing. By screening a library of FDA-approved kinase inhibitors, mTOR, JAK, and Src kinase inhibitors were found to modulate cytokine release. Further in vitro and in vivo experiments confirmed these findings and supported the evaluation of these inhibitors as a treatment to prevent cytokine release syndrome (CRS).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Gabrielle Leclercq, Nathalie Steinhoff, Helene Haegel, Donata De Marco, Marina Bacac, Christian Klein
Summary: T cell engaging therapies redirect T cells towards tumor cells, leading to cytotoxicity. However, this can trigger a release of pro-inflammatory cytokines causing Cytokine Release Syndrome (CRS), which remains a major safety concern. Mitigation strategies are necessary to reduce cytokine release while maintaining efficacy. Tyrosine kinase inhibitors are emerging as a potential strategy for managing CRS symptoms.
Review
Oncology
Andrew Davies, Arnon P. Kater, Jeff P. Sharman, Stephan Stilgenbauer, Umberto Vitolo, Christian Klein, Joana Parreira, Gilles Salles
Summary: The type II anti-CD20 antibody obinutuzumab has shown improved efficacy compared to rituximab in the treatment of indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL). Ongoing research is focusing on biomarkers and developing chemotherapy-free regimens involving obinutuzumab.
Article
Cell Biology
Ester Fagnano, Swati Pendharkar, Madyson Colton, Philip N. Jones, Marta Crespi Sallan, Tetyana Klymenko, Andrejs Braun, Christian Klein, Jamie Honeychurch, Eleanor J. Cheadle, Timothy M. Illidge
Summary: This study showed that contact between tumor cells and stromal cells inhibits the effector functions of Obinutuzumab, highlighting the potential for improved therapies targeting the microenvironment to enhance patient outcomes in B-cell malignancies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Medicine, Research & Experimental
Marlena Surowka, Wolfgang Schaefer, Christian Klein
Summary: CrossMab technology, introduced in 2011, enables correct light-chain and heavy-chain association in bispecific antibodies and has become one of the most mature and widely applied technologies in the field. Multiple bispecific antibodies based on CrossMab technology have entered clinical trials, demonstrating potential therapeutic value in different disease settings.
Meeting Abstract
Oncology
Stephan Wullschleger, Melanie Tichet, Laura Codarri-Deak, Pablo Umana, Christian Klein, Douglas Hanahan