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Improved physical stability of an Antibody Drug Conjugate using Host-Guest chemistry.

07:00 EST 3rd December 2019 | BioPortfolio

Summary of "Improved physical stability of an Antibody Drug Conjugate using Host-Guest chemistry."

Antibody Drug Conjugates (ADCs) are an emerging class of biopharmaceutical products for oncology, with the cytotoxic Pyrrol-oBenzoDiazepine (PBD) family of 'warheads' well established in the clinic. While PBDs offer high potency, they are also characterized by their hydrophobicity which can make formulation of the ADC challenging. Several approaches have been investigated to improve the physico-chemical properties of PBD-containing ADCs and herein a supramolecular approach was explored using cucurbit[8]uril (CB[8]). The ability of CB[8] to simultaneously encapsulate two guests was exploited to incorporate a 12-mer poly-ethylene glycol harboring a methyl-viologen moiety at one terminus (MV-PEG12), together with a PBD harboring an indole moiety at the C'2 position (SG3811). This formulation approach successfully introduced a hydrophilic PEG to mask the hydrophobicity of SG3811, improving the physical stability of the ADC while avoiding any loss of potency related to chemical modification.

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Name: Bioconjugate chemistry
ISSN: 1520-4812
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