Article
Gastroenterology & Hepatology
Honglin Jiang, Tristan Courau, Joseph Borison, Alexa J. Ritchie, Aaron T. Mayer, Matthew F. Krummel, Eric A. Collisson
Summary: MEK and autophagy co-inhibition coupled with CD40 agonism activates the STING/type I interferon pathway and enhances immunogenicity of tumor-associated macrophages in pancreatic ductal adenocarcinoma (PDA) cells. This treatment strategy achieves cytotoxic T-cell activation and enhances antitumor immunity in an immunologically cold mouse PDA model.
Article
Immunology
Catalina Lee-Chang, Jason Miska, David Hou, Aida Rashidi, Peng Zhang, Rachel A. Burga, Ignacio Jusue-Torres, Ting Xiao, Victor A. Arrieta, Daniel Y. Zhang, Aurora Lopez-Rosas, Yu Han, Adam M. Sonabend, Craig M. Horbinski, Roger Stupp, Irina V. Balyasnikova, Maciej S. Lesniak
Summary: The B-Vax vaccine developed in this study showed significant effects in activating autologous CD8(+) T cells and killing GBM cells, achieving an 80% tumor eradication rate in experimental animals.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Meredith L. Stone, Jesse Lee, Veronica M. Herrera, Kathleen Graham, Jae W. Lee, Austin Huffman, Heather Coho, Evan Tooker, Max Myers, Michael Giannone, Yan Li, Thomas H. Buckingham, Kristen B. Long, Gregory L. Beatty
Summary: Agonist CD40 antibodies in combination with chemotherapy can lead to systemic cytokine release, liver transaminase elevations, and chemotherapy-induced hepatotoxicity. However, neutralization of TNF can mitigate liver sensitivity to toxicity induced by anti-CD40, without affecting antitumor efficacy.
Article
Chemistry, Multidisciplinary
Chang-ling Gu, Hai-xia Zhu, Lan Deng, Xiao-qing Meng, Kai Li, Wei Xu, Le Zhao, Yue-qin Liu, Zhen-ping Zhu, Hao-min Huang
Summary: The study developed a bispecific antibody targeting PD1 and HER2, showing high affinities and potent antitumor activities in vitro and in vivo. The BsAb also demonstrated both HER2 and PD1 blockade activities and was effective in killing HER2-positive tumor cells through antibody-dependent cellular cytotoxicity.
ACTA PHARMACOLOGICA SINICA
(2022)
Review
Biochemistry & Molecular Biology
Isabell Lang, Olena Zaitseva, Harald Wajant
Summary: Inhibitory targeting of the CD40L-CD40 system is a promising therapeutic option in organ transplantation and autoimmune diseases. Lack of Fc gamma receptor (Fc gamma R)-binding is crucial for the development of safe inhibitory antibodies targeting CD40L or CD40. Recent clinical studies have shown that blocking CD40 antibodies not interacting with Fc gamma Rs are well tolerated and have initial clinical efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Emily Phung, Lauren A. Chang, Maryam Mukhamedova, Lijuan Yang, Deepika Nair, Scott A. Rush, Kaitlyn M. Morabito, Jason S. McLellan, Ursula J. Buchholz, John R. Mascola, Michelle C. Crank, Grace Chen, Barney S. Graham, Tracy J. Ruckwardt
Summary: RSV pre-F vaccination results in expansion and activation of RSV and HMPV F-specific B cells that contribute to long-term pneumovirus immunity.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Cesare Di Nitto, Ettore Gilardoni, Jacqueline Mock, Lisa Nadal, Tobias Weiss, Michael Weller, Frauke Seehusen, Chiara Libbra, Emanuele Puca, Dario Neri, Roberto De Luca
Summary: In this study, a novel fusion protein (L19-IFN gamma KRG) is described, which selectively localizes to tumors and regains biological activity upon antigen binding. This fusion protein showed tumor growth inhibition and increased intratumoral concentration of T cells and NK cells in murine cancer models, with a better effect when used in combination with anti-PD-1 therapy.
Article
Multidisciplinary Sciences
Michael Lacy, Christina Buerger, Annelie Shami, Maiwand Ahmadsei, Holger Winkels, Katrin Nitz, Claudia M. van Tiel, Tom T. P. Seijkens, Pascal J. H. Kusters, Ela Karshovka, Koen H. M. Prange, Yuting Wu, Sanne L. N. Brouns, Sigrid Unterlugauer, Marijke J. E. Kuijpers, Myrthe E. Reiche, Sabine Steffens, Andreas Edsfeldt, Remco T. A. Megens, Johan W. M. Heemskerk, Isabel Goncalves, Christian Weber, Norbert Gerdes, Dorothee Atzler, Esther Lutgens
Summary: The CD40L-CD40 signaling axis plays a role in atherosclerosis. This study investigates the cell-specific functions of the most relevant CD40L-expressing cell types. Deficiency of T cell-derived CD40L reduces and stabilizes plaques through impaired Th1 polarization, while platelet-derived CD40L ameliorates atherothrombosis.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Adnan Deronic, Anneli Nilsson, Mia Thagesson, Doreen Werchau, Karin Enell Smith, Peter Ellmark
Summary: Mitazalimab, a human anti-CD40 agonist antibody, was found to activate antigen-presenting cells, leading to expansion and activation of antigen-specific T cells, ultimately enhancing the anti-tumor efficacy of a model cancer vaccine.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Virology
Iebe Rossey, Ching-Lin Hsieh, Koen Sedeyn, Marlies Ballegeer, Bert Schepens, Jason S. Mclellan, Xavier Saelens
Summary: This study identified a prefusion F-specific VHH that primarily binds to antigenic site I of RSV F. The VHH neutralizes RSV A at subnanomolar concentrations, highlighting a previously underappreciated membrane-proximal region sensitive to neutralization. These findings contribute to insights into the RSV F antigenic map.
JOURNAL OF VIROLOGY
(2021)
Article
Clinical Neurology
Karin Mausner-Fainberg, Moshe Benhamou, Maya Golan, Nadav Bleich Kimelman, Uri Danon, Ehud Marom, Arnon Karni
Summary: Specific blockade of BMP-2/4 signaling pathway promotes differentiation of oligodendrocyte precursor cells, increases the numbers of immature and mature oligodendrocytes while decreasing newly generated astrocytes, accelerates remyelination in demyelinated lesions, and shows therapeutic potential in demyelinating disorders such as multiple sclerosis.
Article
Microbiology
Poonsook Keelapang, Romchat Kraivong, Rojjanaporn Pulmanausahakul, Rungtawan Sriburi, Eakachai Prompetchara, Jutamart Kaewmaneephong, Nicha Charoensri, Pattarakul Pakchotanon, Thaneeya Duangchinda, Piyanan Suparattanagool, Prasit Luangaram, Promsin Masrinoul, Juthathip Mongkolsapaya, Gavin Screaton, Kiat Ruxrungtham, Prasert Auewarakul, Sutee Yoksan, Prida Malasit, Chunya Puttikhunt, Chutitorn Ketloy, Nopporn Sittisombut
Summary: This study describes a blockade-of-binding assay to determine antibodies recognizing particular epitopes in the envelope of dengue virus. The assay showed moderate to strong correlations between epitope-blocking activities and virus-neutralizing antibody titers for each of the four dengue serotypes using blood samples from infected or immunized macaques.
MICROBIOLOGY SPECTRUM
(2023)
Article
Medicine, Research & Experimental
Aixian Zheng, Yanlin Du, Yiru Wang, Youshi Zheng, Zhaoyu Ning, Ming Wu, Cuilin Zhang, Da Zhang, Jingfeng Liu, Xiaolong Liu
Summary: This study introduces a highly stable CD16/PDL1 bi-specific aptamer (CP-bi-apt) that enhances the immune response of NK cells against tumors and reduces the negative impact of PD-L1 over-expression.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Review
Immunology
Avneesh K. Singh, Corbin E. Goerlich, Tianshu Zhang, Billeta G. T. Lewis, Alena Hershfeld, Muhammad M. Mohiuddin
Summary: Effective immune responses require CD40-CD40L costimulatory signaling in transplantation, which plays a vital role in controlling humoral and cellular immunity. Blocking this signaling pathway can inhibit donor-reactive T-cell responses and prolong the survival of transplanted organs.
Review
Biochemistry & Molecular Biology
Qun Zhou
Summary: As antibody-drug conjugates have become crucial for cancer therapy, various approaches have been developed to achieve selective and homogeneous molecules. These methods involve engineering antibodies to introduce specific amino acids or peptides for coupling. In addition to cytotoxic compounds, these techniques can also be applied to conjugate non-cytotoxic compounds, proteins/peptides, glycans, lipids, and nucleic acids. The resulting site-specific antibody conjugates offer potential for proof-of-concept studies and the development of novel therapeutic options.
