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- W4313349701 abstract "Abstract Costimulatory molecules of the CD28 and TNFR superfamilies modulate innate, adaptive, and regulatory immune responses, and therefore agonistic ligands to these receptors have potential to serve as effective immunomodulatory components of therapeutic vaccines. However, the use of costimulatory agonists for vaccines in humans requires the generation of agonists that transduce appropriate stimulatory signals without toxic side effects. We hypothesized that signaling by natural ligands may have better efficacy and safety compared to agonistic Abs. Our laboratory recently developed a novel form of soluble 4-1BB ligand (SA-4-1BBL) which forms functional tetramers/oligomers. SA-4-1BBL demonstrated superior immunostimulatory activity than an agonistic 4-1BB Ab (3H3), and importantly lacked Ab associated toxicity as manifested by greatly enlarged spleen and LNs, non-specific T cell proliferation, hepatitis, and increased T cell and systemic inflammatory cytokine production. Ab associated toxicity did not involve Fc receptor or complement activation, and adoptive transfer studies demonstrate that CD8+ and CD4+ T cells were the direct targets of Ab mediated toxicity. Our findings support further development of this novel form of soluble 4-1BBL as an immunomodulatory component of therapeutic vaccines.NIH (R43 AI071618, R41 CA121665, R44 AI071618, and R43AI074176), KLCRP, and W.M. Keck Foundation." @default.
- W4313349701 created "2023-01-06" @default.
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- W4313349701 date "2009-04-01" @default.
- W4313349701 modified "2023-09-30" @default.
- W4313349701 title "A novel form of 4-1BBL demonstrates better immunomodulatory activity than an agonistic anti-4-1BB Ab without Ab associated severe toxicity (41.4)" @default.
- W4313349701 doi "https://doi.org/10.4049/jimmunol.182.supp.41.4" @default.
- W4313349701 hasPublicationYear "2009" @default.
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