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- W4313431383 abstract "Abstract Fibroblast activation protein (FAP) is a cell surface serine protease that is highly expressed on reactive stromal fibroblasts, such as cancer-associated fibroblasts (CAFs), and generally absent in healthy adult tissues. FAP expression in the tumor stroma has been detected in more than 90% of all carcinomas, rendering CAFs excellent target cells for a tumor site-specific adenoviral delivery of cancer therapeutics. Here, we present a tropism-modified human adenovirus 5 (Ad5) vector that targets FAP through trivalent, designed ankyrin repeat protein (DARPin)-based retargeting adapters. We describe the development and validation of these adapters via cell-based screening assays and demonstrate adapter-mediated Ad5 retargeting to FAP + fibroblasts in vitro and in vivo . We further show efficient in vivo delivery and in-situ production of a therapeutic payload by CAFs in the tumor microenvironment (TME), resulting in attenuated tumor growth. We thus propose using our FAP-Ad5 vector to convert CAFs into a ‘biofactory’, secreting encoded cancer therapeutics into the TME to enable a safe and effective cancer treatment." @default.
- W4313431383 created "2023-01-06" @default.
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- W4313431383 date "2022-12-19" @default.
- W4313431383 modified "2023-09-26" @default.
- W4313431383 title "FAP-retargeted Ad5 enables<i>in vivo</i>gene delivery to stromal cells in the tumor microenvironment" @default.
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- W4313431383 doi "https://doi.org/10.1101/2022.12.19.520931" @default.
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