Therapeutic monoclonal antibodies are the fastest growing class of biological therapeutics for the treatment of various cancers and inflammatory disorders. In cancer immunotherapy, some IgG1 antibodies rely on the Fc-mediated immune effector function, antibody-dependent cellular cytotoxicity (ADCC), as the major mode of action to deplete tumor cells. It is well-known that this effector function is modulated by the N-linked glycosylation in the Fc region of the antibody. In particular, absence of core fucose on the Fc N-glycan has been shown to increase IgG1 Fc binding affinity to the FcγRIIIa present on immune effector cells such as natural killer cells and lead to enhanced ADCC activity. As such, various strategies have focused on producing afucosylated antibodies to improve therapeutic efficacy. This review discusses the relevance of antibody core fucosylation to ADCC, different strategies to produce afucosylated antibodies, and an update of afucosylated antibody drugs currently undergoing clinical trials as well as those that have been approved.

Aligned poly(L-lactide) (PLLA) electrospun nanofibers of different molecular weights (M w = 100K, 300K, and 700K) were collected using a rotating disk at take-up velocities of 63, 630, and 1890 m/min. Structural development within the spun fibers was examined. Enhanced crystallinities were observed within the fibers spun at elevated take-up velocities, from the polymers with increased M w . Mechanical properties were evaluated using the single nanofiber tensile test. Despite exhibiting remarkable crystalline and amorphous orientation, the fibers prepared from polymer of molecular weight, 700K, displayed a significant drop in tensile strength when a take-up velocity of 1890 m/min was used to stretch and align the fibers. The finding suggests that an optimum processing condition exists in the preparation of mechanically superior PLLA fiber electrospun from different molecular weight. This study has also collected aligned nanofibers electrospun from poly(L-lactide) (PLLA)/poly(D-lactide) (PDLA) blended solutions at take-up velocity of 630 m/min. Highest stereocomplexation activity was observed within the fibers spun from PLLA/PDLA blend solution with weight concentration 50/50 wt/wt. The tensile results highlighted that, among the various blend ratios spun with take-up velocity of 630 m/min, the highest tensile strength was observed for the fibers obtained at a blend ratio of 50/50 wt/wt.

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Removal of core fucose from N-glycans attached to human IgG1 significantly enhances its affinity for the receptor FcγRIII and thereby dramatically improves its antibody-dependent cellular cytotoxicity activity. While previous works have shown that inactivation of fucosyltransferase 8 results in mutants capable of producing fucose-free antibodies, we report here the use of genome editing techniques, namely ZFNs, TALENs and the CRISPR-Cas9, to inactivate the GDP-fucose transporter (SLC35C1) in Chinese hamster ovary (CHO) cells. A FACS approach coupled with a fucose-specific lectin was developed to rapidly isolate SLC35C1-deficient cells. Mass spectrometry analysis showed that both EPO-Fc produced in mutants arising from CHO-K1 and anti-Her2 antibody produced in mutants arising from a pre-existing antibody-producing CHO-HER line lacked core fucose. Lack of functional SLC35C1 in these cells does not affect cell growth or antibody productivity. Our data demonstrate that inactivating Slc35c1 gene represents an alternative approach to generate CHO cells for production of fucose-free antibodies.