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10.1074/jbc.M116.733600 http://scihub22266oqcxt.onion/10.1074/jbc.M116.733600 C5104912!5104912!27650494     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27650494&cmd=llinks): Failed to open stream: HTTP request failed! 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A Novel Fusion of ALT-803 (Interleukin (IL)-15 Superagonist) with an Antibody Demonstrates Antigen-specific Antitumor Responses* |pdf=|usr=}}{{27650494}} gab.com Text A Novel Fusion of ALT-803 (Interleukin (IL)-15 Superagonist) with an Antibody Demonstrates Antigen-specific Antitumor Responses* JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=27650494 #FOAvip IL-15 and its receptor ? (IL-15R?) are co-expressed on antigen-presenting cells, allowing transpresentation of IL-15 to immune cells bearing IL-2R??C and stimulation of effector immune responses. We reported previously that the high-affinity interactions between an IL-15 superagonist (IL-15N72D) and the extracellular IL-15R? sushi domain (IL-15R?Su) could be exploited to create a functional scaffold for the design of multivalent disease-targeted complexes. The IL-15N72D·IL-15R?SuFc complex, also known as ALT-803, is a multimeric complex constructed by fusing IL-15N72D·IL-15R?Su to the Fc domain of IgG1. ALT-803 is an IL-15 superagonist complex that has been developed as a potent antitumor immunotherapeutic agent and is in clinical trials. Here we describe the creation of a novel fusion molecule, 2B8T2M, using the ALT-803 scaffold fused to four single chains of the tumor-targeting monoclonal antibody rituximab. This molecule displays trispecific binding activity through its recognition of the CD20 molecule on tumor cells, stimulation via IL-2R??C displayed on immune effector cells, and binding to Fc? receptors on natural killer cells and macrophages. 2B8T2M activates natural killer cells to enhance antibody-dependent cellular cytotoxicity, mediates complement-dependent cytotoxicity, and induces apoptosis of B-lymphoma cells. Compared with rituximab, 2B8T2M exhibits significantly stronger antitumor activity in a xenograft SCID mouse model and depletes B cells in cynomolgus monkeys more efficiently. Thus, ALT-803 can be modified as a functional scaffold for creating multispecific, targeted IL-15-based immunotherapeutic agents and may serve as a novel platform to improve the antitumor activity and clinical efficacy of therapeutic antibodies. Twit Text FOAVip A Novel Fusion of ALT-803 (Interleukin (IL)-15 Superagonist) with an Antibody Demonstrates Antigen-specific Antitumor Responses* ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=27650494 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27650494 #FOAvip English Wikipedia <ref>{{Cite pmid|27650494}}</ref> A Novel Fusion of ALT-803 (Interleukin (IL)-15 Superagonist) with an Antibody Demonstrates Antigen-specific Antitumor Responses* #MMPMID27650494 Liu B; Kong L; Han K; Hong H; Marcus WD; Chen X; Jeng EK; Alter S; Zhu X; Rubinstein MP; Shi S; Rhode PR; Cai W; Wong HC J Biol Chem 2016[Nov]; 291 (46): 23869-81 PMID27650494show ga IL-15 and its receptor ? (IL-15R?) are co-expressed on antigen-presenting cells, allowing transpresentation of IL-15 to immune cells bearing IL-2R??C and stimulation of effector immune responses. We reported previously that the high-affinity interactions between an IL-15 superagonist (IL-15N72D) and the extracellular IL-15R? sushi domain (IL-15R?Su) could be exploited to create a functional scaffold for the design of multivalent disease-targeted complexes. The IL-15N72D·IL-15R?SuFc complex, also known as ALT-803, is a multimeric complex constructed by fusing IL-15N72D·IL-15R?Su to the Fc domain of IgG1. ALT-803 is an IL-15 superagonist complex that has been developed as a potent antitumor immunotherapeutic agent and is in clinical trials. Here we describe the creation of a novel fusion molecule, 2B8T2M, using the ALT-803 scaffold fused to four single chains of the tumor-targeting monoclonal antibody rituximab. This molecule displays trispecific binding activity through its recognition of the CD20 molecule on tumor cells, stimulation via IL-2R??C displayed on immune effector cells, and binding to Fc? receptors on natural killer cells and macrophages. 2B8T2M activates natural killer cells to enhance antibody-dependent cellular cytotoxicity, mediates complement-dependent cytotoxicity, and induces apoptosis of B-lymphoma cells. Compared with rituximab, 2B8T2M exhibits significantly stronger antitumor activity in a xenograft SCID mouse model and depletes B cells in cynomolgus monkeys more efficiently. Thus, ALT-803 can be modified as a functional scaffold for creating multispecific, targeted IL-15-based immunotherapeutic agents and may serve as a novel platform to improve the antitumor activity and clinical efficacy of therapeutic antibodies. äA Novel Fusion of ALT-803 (Interleukin (IL)-15 Superagonist) with an A(epmc).pdf DeepDyve Pubget Overpricing