2022
DOI: 10.3390/pharmaceutics14081524
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Intra-Domain Cysteines (IDC), a New Strategy for the Development of Original Antibody Fragment–Drug Conjugates (FDCs)

Abstract: Antibody–drug conjugates (ADCs) derived from a full immunoglobulin-G (IgG) are associated with suboptimal solid-tumor penetration and Fc-mediated toxicities. Antibody fragment–drug conjugates (FDCs) could be an alternative. Nevertheless, innovative solutions are needed to implant cysteines as conjugation sites in the single-chain fragment variable (scFv) format, which is the backbone from which many other antibody formats are built. In addition, the bioconjugation site has the utmost importance to optimize the… Show more

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Cited by 4 publications
(3 citation statements)
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“…As the name suggests, FDCs use smaller antibody fragments instead of larger antibody molecules [332]. It is generally believed that antibody fragments are relatively easy to detect and that a higher DAR can be achieved using biotechnology [333].…”
Section: Antibody Fragment-drug Conjugates (Fdcs)mentioning
confidence: 99%
“…As the name suggests, FDCs use smaller antibody fragments instead of larger antibody molecules [332]. It is generally believed that antibody fragments are relatively easy to detect and that a higher DAR can be achieved using biotechnology [333].…”
Section: Antibody Fragment-drug Conjugates (Fdcs)mentioning
confidence: 99%
“…However, no antibody fragments have been approved for cancer therapy, including NSCLC. The structural advantages of antibody fragments cannot be ignored, and breakthroughs are being made with antibody fragment-drug conjugates (AFDCs) based on antibody fragments ( Liu et al, 2019a ; Jolivet et al, 2022 ), while clinical trials have been conducted for NSCLC (NCT01221675).…”
Section: Antibody Therapy In Nsclcmentioning
confidence: 99%
“…In fact, ADCs prolonged half-life promoted by the neonatal Fc receptor (FcRn) increases exposure to healthy tissues, while FcγR cross-reacts with endothelial and immune cells, both of which are biological processes related to off-target toxicity 6 . A promising alternative to the conventional immunoglobulin (IgG) to produce ADCs are smaller formats, such as single-domain antibodies (sdAbs), single-chain antibody fragments (scFvs) and minibodies 18 , 19 . sdAbs are presently the smallest functional antigen-binding fragments, only consisting of a VH or VL, that can be obtained from conventional IgGs.…”
Section: Introductionmentioning
confidence: 99%