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- W4313356093 abstract "Abstract IL-15 and its receptor α (IL-15Ra) are co-expressed in antigen presenting cells allowing trans-presentation of IL-15 to immune cells bearing IL-2Rβγc and stimulation of effector immune responses. We have demonstrated that an IL-15 superagonist:IL-15Rα-Fc complex (ALT-803) is capable of stimulating T cell and NK cell responses. We have reported that ALT-803 could be exploited to create a functional scaffold for the design of multivalent disease-targeted complexes (Liu et al, J. Biol. Chem. 2016 291: 23869). The lead molecule based on anti-CD20 rituximab is currently in pre-clinical development. In this study, this approach was further optimized by generating an IL-15 superagonist:IL-15Rα-Fc complex (2B8T3M) comprising two anti-human CD20 scFv domains and two anti-human CD3 scFv domains. 2B8T3M molecules exhibit CD3, CD20, Fc-receptor and IL-15Rbgc tetra-specific binding activities and IL-15 bioactivity. In contrast to 2B8T2M which redirects NK cells to lyse CD20+ B-lymphoma cells (ADCC), 2B8T3M was capable of redirecting both CD8+ T cells via the anti-CD3 scFv domains and NK cells via the Fc domain against CD20+ Daudi cells. In order to investigate antitumor activities in vivo of the tetra-specific molecules in immunocompetent mouse, we have also constructed and generated mouse CD3/CD19-binding T3M complexes. Antitumor efficacy of these molecules is being assessed in mouse A20 B cell lymphoma model. These findings suggest that tetra-specific T3M complexes may serve as novel, T-cell based targeted immunotherapeutics for treating cancer." @default.
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- W4313356093 date "2017-05-01" @default.
- W4313356093 modified "2023-10-18" @default.
- W4313356093 title "Novel antitumor complexes of bispecific antibodies using ALT-803 as a scaffold demonstrate Tetra-specific binding activities" @default.
- W4313356093 doi "https://doi.org/10.4049/jimmunol.198.supp.120.12" @default.
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