Silverback therapeutics3/29/2023 “In preclinical studies, SBT6050 demonstrated a broad therapeutic window and this profile has enabled the selection of a first-in-human starting dose projected to be pharmacologically active,” Odegard added, “SBT6050 is designed for systemic administration and tumor-localized activation of myeloid cells, in order to circumvent toxicities associated with untargeted myeloid cell agonists,” said Valerie Odegard, Ph.D., Silverback’s chief scientific officer. The approach of myeloid cell activation and reprogramming in the tumor microenvironment has emerged as a promising therapeutic approach. The investigational agent is designed to activate human myeloid cells in tumors expressing moderate or high levels of HER2. SBT6050, a novel ImmunoTAC™ therapeutic being developed by Silverback Therapeutics, includes a HER2-directed antibody conjugated to a potent and specific small molecule toll-like receptor 8 (TLR8) agonist, with activity localized to HER2-expressing tumor sites. TLR8 is highly expressed in myeloid cells that are prevalent in human tumors and TLR8 agonism can potently activate a broad spectrum of anti-tumor immune mechanisms. Īctivation of toll-like receptor 8 (TLR8) enhances natural killer(NK-) cell activation, increases antibody-dependent cell-mediated cytotoxicity and induces Th1 polarizing cytokines. TLR-dependent recognition of PAMPs leads to activation of the innate immune system, which subsequently leads to the activation of antigen-specific adaptive immunity. TLRs recognize specific patterns of microbial components, called pathogen-associated molecular patterns (PAMPs). The innate immune system recognizes invading microorganisms by a phylogenetically conserved family of proteins PRRs of which toll-like receptors (TLRs) are one of the most important.
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