FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2049743251> ?p ?o ?g. }

• W2049743251 endingPage "881" @default.
• W2049743251 startingPage "872" @default.
• W2049743251 abstract "Knobs-into-holes is a well-validated heterodimerization technology for the third constant domain of an antibody. This technology has been used to produce a monovalent IgG for clinical development (onartuzumab) and multiple bispecific antibodies.1,2 The most advanced uses of this approach, however, have been limited to E. coli as an expression host to produce non-glycosylated antibodies. Here, we applied the technology to mammalian host expression systems to produce glycosylated, effector-function competent heterodimeric antibodies. In our mammalian host system, each arm is secreted as a heavy chain-light chain (H-L) fragment with either the knob or hole mutations to allow for preferential heterodimer formation in vitro with low levels of homodimer contaminants. Like full antibodies, the secreted H-L fragments undergo Fc glycosylation in the endoplasmic reticulum. Using a monospecific anti-CD20 antibody, we show that full antibody-dependent cell-mediated cytotoxicity (ADCC) activity can be retained in the context of a knobs-into-holes heterodimer. Because the knobs-into-holes mutations convert the Fc into an asymmetric heterodimer, this technology was further used to systematically explore asymmetric recognition of the Fc. Our results indicate that afucosylation of half the heterodimer is sufficient to produce ADCC-enhancement similar to that observed for a fully afucosylated antibody with wild-type Fc. However, the most dramatic effect on ADCC activity is observed when two carbohydrate chains are present rather than one, regardless of afucosylation state." @default.
• W2049743251 created "2016-06-24" @default.
• W2049743251 creator A5000041864 @default.
• W2049743251 creator A5002138594 @default.
• W2049743251 creator A5006272129 @default.
• W2049743251 creator A5014172121 @default.
• W2049743251 creator A5023502262 @default.
• W2049743251 creator A5047150251 @default.
• W2049743251 creator A5052163052 @default.
• W2049743251 creator A5083581319 @default.
• W2049743251 creator A5084345191 @default.
• W2049743251 date "2013-11-01" @default.
• W2049743251 modified "2023-10-15" @default.
• W2049743251 title "Knobs-into-holes antibody production in mammalian cell lines reveals that asymmetric afucosylation is sufficient for full antibody-dependent cellular cytotoxicity" @default.
• W2049743251 cites W1518819083 @default.
• W2049743251 cites W1529809181 @default.
• W2049743251 cites W1825768998 @default.
• W2049743251 cites W1831036856 @default.
• W2049743251 cites W1969824500 @default.
• W2049743251 cites W1976652440 @default.
• W2049743251 cites W1986197388 @default.
• W2049743251 cites W1992886596 @default.
• W2049743251 cites W2001483547 @default.
• W2049743251 cites W2006264959 @default.
• W2049743251 cites W2028793480 @default.
• W2049743251 cites W2029669166 @default.
• W2049743251 cites W2030621571 @default.
• W2049743251 cites W2032552806 @default.
• W2049743251 cites W2035753258 @default.
• W2049743251 cites W2037007095 @default.
• W2049743251 cites W2044360617 @default.
• W2049743251 cites W2063840206 @default.
• W2049743251 cites W2078353854 @default.
• W2049743251 cites W2079579628 @default.
• W2049743251 cites W2084136419 @default.
• W2049743251 cites W2084748765 @default.
• W2049743251 cites W2090212988 @default.
• W2049743251 cites W2091300510 @default.
• W2049743251 cites W2115571948 @default.
• W2049743251 cites W2121107218 @default.
• W2049743251 cites W2128402413 @default.
• W2049743251 cites W2130350426 @default.
• W2049743251 cites W2133626640 @default.
• W2049743251 cites W2137354517 @default.
• W2049743251 cites W2159861616 @default.
• W2049743251 cites W2168356942 @default.
• W2049743251 doi "https://doi.org/10.4161/mabs.26307" @default.
• W2049743251 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3896601" @default.
• W2049743251 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23995614" @default.
• W2049743251 hasPublicationYear "2013" @default.
• W2049743251 type Work @default.
• W2049743251 sameAs 2049743251 @default.
• W2049743251 citedByCount "63" @default.
• W2049743251 countsByYear W20497432512014 @default.
• W2049743251 countsByYear W20497432512015 @default.
• W2049743251 countsByYear W20497432512016 @default.
• W2049743251 countsByYear W20497432512017 @default.
• W2049743251 countsByYear W20497432512018 @default.
• W2049743251 countsByYear W20497432512019 @default.
• W2049743251 countsByYear W20497432512020 @default.
• W2049743251 countsByYear W20497432512021 @default.
• W2049743251 countsByYear W20497432512022 @default.
• W2049743251 countsByYear W20497432512023 @default.
• W2049743251 crossrefType "journal-article" @default.
• W2049743251 hasAuthorship W2049743251A5000041864 @default.
• W2049743251 hasAuthorship W2049743251A5002138594 @default.
• W2049743251 hasAuthorship W2049743251A5006272129 @default.
• W2049743251 hasAuthorship W2049743251A5014172121 @default.
• W2049743251 hasAuthorship W2049743251A5023502262 @default.
• W2049743251 hasAuthorship W2049743251A5047150251 @default.
• W2049743251 hasAuthorship W2049743251A5052163052 @default.
• W2049743251 hasAuthorship W2049743251A5083581319 @default.
• W2049743251 hasAuthorship W2049743251A5084345191 @default.
• W2049743251 hasBestOaLocation W20497432511 @default.
• W2049743251 hasConcept C109316439 @default.
• W2049743251 hasConcept C125823703 @default.
• W2049743251 hasConcept C151730666 @default.
• W2049743251 hasConcept C153911025 @default.
• W2049743251 hasConcept C158617107 @default.
• W2049743251 hasConcept C159654299 @default.
• W2049743251 hasConcept C170493617 @default.
• W2049743251 hasConcept C175656101 @default.
• W2049743251 hasConcept C185592680 @default.
• W2049743251 hasConcept C202751555 @default.
• W2049743251 hasConcept C203014093 @default.
• W2049743251 hasConcept C2777313579 @default.
• W2049743251 hasConcept C2779343474 @default.
• W2049743251 hasConcept C36394416 @default.
• W2049743251 hasConcept C40677261 @default.
• W2049743251 hasConcept C51785407 @default.
• W2049743251 hasConcept C55493867 @default.
• W2049743251 hasConcept C86803240 @default.
• W2049743251 hasConcept C95444343 @default.
• W2049743251 hasConceptScore W2049743251C109316439 @default.
• W2049743251 hasConceptScore W2049743251C125823703 @default.
• W2049743251 hasConceptScore W2049743251C151730666 @default.
• W2049743251 hasConceptScore W2049743251C153911025 @default.
• W2049743251 hasConceptScore W2049743251C158617107 @default.

• next