Engineering of an EpCAM-targeting cyclic peptide to improve the EpCAM-mediated cellular internalization and tumor accumulation of a peptide-fused antibody

Park, Seong-Wook; Jun, Sei-Yong; Kim, Jisun; Kim, Yong‐Sung

doi:10.1016/j.bbrc.2021.08.021

Cited by 8 publications

(1 citation statement)

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“…An EpCAM-binding variant of inRas37 for treatment of pancreatic cancers was developed by simply swapping the integrin-binding peptide with an EpCAM-recognizing cyclic peptide [ 259 ]. Optimization of this EpCAM-targeting peptide resulted in low nanomolar affinity and enhanced accumulation in EpCAM-expressing tumors compared to the original integrin αvβ3/αvβ5 targeting peptides [ 260 ]. In addition, hybrid “targeting penetrating peptides” with dual tumor targeting and internalization functions have been published [ 261 ].…”

Section: Intracellular Protein Delivery: Challenges and Perspectivesmentioning

confidence: 99%

Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications

Chan,

Tsourkas

2024

BME Front

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Protein biologics are powerful therapeutic agents with diverse inhibitory and enzymatic functions. However, their clinical use has been limited to extracellular applications due to their inability to cross plasma membranes. Overcoming this physiological barrier would unlock the potential of protein drugs for the treatment of many intractable diseases. In this review, we highlight progress made toward achieving cytosolic delivery of recombinant proteins. We start by first considering intracellular protein delivery as a drug modality compared to existing Food and Drug Administration-approved drug modalities. Then, we summarize strategies that have been reported to achieve protein internalization. These techniques can be broadly classified into 3 categories: physical methods, direct protein engineering, and nanocarrier-mediated delivery. Finally, we highlight existing challenges for cytosolic protein delivery and offer an outlook for future advances.

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Section: Intracellular Protein Delivery: Challenges and Perspectivesmentioning

confidence: 99%