Interleukin (IL)-15 plays an important role in the communication between immune cells. It delivers its signal through different modes involving three receptor chains: IL-15Rα, IL-2Rβ and IL-2Rγc. The combination of the different chains result in the formation of IL-15Rα/IL-2Rβ/γc trimeric or IL-2Rβ/γc dimeric receptors. In this study, we have investigated the role of the IL-15Rα chain in stabilizing the cytokine in the IL-2Rβ/γc dimeric receptor. By analyzing the key amino acid residues of IL-15 facing IL-2Rβ, we provide evidence of differential interfaces in the presence or in the absence of membrane-anchored IL-15Rα. Moreover, we found that the anchorage of IL-15Rα to the cell surface regardless its mode of presentation - i.e. or - is crucial for complete signaling. These observations show how the cells can finely modulate the intensity of cytokine signaling through the quality and the level of expression of the receptor chains.
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http://dx.doi.org/10.1242/jcs.236802 | DOI Listing |
Cancer Immunol Res
January 2025
Light Chain Bioscience - Novimmune SA, Geneva, Switzerland.
Despite advances in cancer immunotherapy, such as targeting the PD-1/PD-L1 axis, a substantial number of patients harbor tumors that are resistant or relapse. Selective engagement of T-cell co-stimulatory molecules with bispecific antibodies may offer novel therapeutic options by enhancing signal 1-driven activation occurring via T-cell receptor engagement. In this study, we report the development and preclinical characterization of NI-3201, a PD-L1×CD28 bispecific antibody generated on the κλ-body platform that was designed to promote T-cell activity and antitumor function through a dual mechanism of action.
View Article and Find Full Text PDFJ Anim Sci
January 2025
Department of Animal and Food Sciences, Texas Tech University, Lubbock, TX USA.
The number of beef × dairy animals entering feedlots has increased, but the response of beef × dairy cattle to growth-promoting implants has not been well characterized. The objective of this study was to evaluate the effects of breed type and implant administration on live performance, carcass characteristics, sera metabolites, and immunohistochemical (IHC) outcomes. Forty-eight steers (average body weight [BW] = 417±22 kg) were sorted by breed into groups of predominantly Angus (B), black-hided beef × primarily Holstein (B×D), or Holstein (D), and half of the steers within each breed type were administered a steroidal implant.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Immunology and Theranostics, City of Hope, Duarte, CA, United States.
Introduction: Although CAR-T cell therapy has limited efficacy against solid tumors, it has been hypothesized that prior treatment with Image-Guided Radiation Therapy (IGRT) would increase CAR-T cell tumor infiltration, leading to improved antigen specific expansion of CAR-T cells.
Methods: To test this hypothesis in a metastatic triple negative breast cancer (TNBC) model, we engineered two anti-CEA single-chain Fab (scFab) CAR-T cells with signaling domains from CD28zeta and 4-1BBzeta, and tested them and .
Results: The anti-CEA scFab CAR-T cells generated from three different human donors demonstrated robust expression, expansion, and lysis of only CEA-positive TNBC cells, with the CD28z-CAR-T cells showing the highest cytotoxicity.
Front Pharmacol
December 2024
Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Introduction: In the last decades, the recombinant tissue plasminogen activator alteplase has been the standard fibrinolytic treatment of acute myocardial infarction, pulmonary embolism, and acute ischemic stroke. An optimized version of alteplase, tenecteplase, has been developed by exchanging six amino acids to increase half-life, achieve higher fibrin selectivity and increase resistance to plasminogen activator inhibitor-1. Meanwhile, several products containing tenecteplase exist.
View Article and Find Full Text PDFJ Med Chem
January 2025
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
The development of dual prostaglandin E receptors 2/4 (EP2/EP4) antagonists represents an attractive strategy for cancer immunotherapy. Herein, a series of 4,7-dihydro-5-thieno[2,3-]pyran derivatives with potent EP2/EP4 dual antagonism were discovered by fine-tuned structural modifications. The biphenyl side chain was found to be the key pharmacophore for the transition from EP4 antagonism to EP2/EP4 dual antagonism.
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