Lepidopteran cells, an alternative for the production of recombinant antibodies?

Cérutti, Martine; Golay, Joseé

doi:10.4161/mabs.19942

Cited by 20 publications

(11 citation statements)

References 152 publications

(204 reference statements)

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“…High mannose-type N-glycans contain from five to nine mannose residues and are found on antibodies produced in mammalian cells, 12 yeast, 13 insect cells 14 and plants, 15 but only at a very low level in normal human antibodies 16 . High mannose glycans on the Fc region of therapeutic IgG antibodies increase serum clearance in humans 17 , 18 .…”

Section: Effect Of Glycosylation On Immunogenicity or Clearancementioning

confidence: 99%

Marketing approval of mogamulizumab

Beck

Reichert

2012

mAbs

194

106

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Therapeutic properties of antibodies strongly depend on the composition of their glycans. Most of the currently approved antibodies are produced in mammalian cell lines, which yield mixtures of different glycoforms that are close to those of humans, but not fully identical. Glyco-engineering is being developed as a method to control the composition of carbohydrates and to enhance the pharmacological properties of mAbs. The recent approval in Japan of mogamulizumab (POTELIGEO®), the first glyco-engineered antibody to reach the market, is a landmark in the field of therapeutic antibodies. Mogamulizumab is a humanized mAb derived from Kyowa Hakko Kirin’s POTELLIGENT® technology, which produces antibodies with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity. The approval was granted April 30, 2012 by the Japanese Ministry of Health, Labour and Welfare for patients with relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma.

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Section: Effect Of Glycosylation On Immunogenicity or Clearancementioning

confidence: 99%

Marketing approval of mogamulizumab

Beck

Reichert

2012

mAbs

194

106

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“…Glycoproteins produced in this system are functional and recombinant Abs can exhibit all effectors functions (42). Through PCR, the correct mutations were introduced into the cDNA encoding the CH1 and CL domains of anti-CD5.…”

Section: Validation Of Cr3 and Mut4 Mutations In Mab1mentioning

confidence: 99%

“…Recombinant baculoviruses expressing WT or mutated chimeric, monospecific anti-CD5 Abs were obtained as described previously (42). For the construction of recombinant viruses expressing BsAbs, a new bacmid allowing the insertion of three genes into the viral genome was used (43), generating a triple-recombinant baculovirus coexpressing equimolar amount of the 3 chains.…”

Section: Generation Of Recombinant Virusesmentioning

confidence: 99%

Design and Validation of a Novel Generic Platform for the Production of Tetravalent IgG1-like Bispecific Antibodies

Golay

Choblet

Iwaszkiewicz

et al. 2016

The Journal of Immunology

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We have designed and validated a novel generic platform for production of tetravalent IgG1-like chimeric bispecific Abs. The VH-CH1-hinge domains of mAb2 are fused through a peptidic linker to the N terminus of mAb1 H chain, and paired mutations at the CH1-CL interface mAb1 are introduced that force the correct pairing of the two different free L chains. Two different sets of these CH1-CL interface mutations, called CR3 and MUT4, were designed and tested, and prototypic bispecific Abs directed against CD5 and HLA-DR were produced (CD5xDR). Two different hinge sequences between mAb1 and mAb2 were also tested in the CD5xDR-CR3 or -MUT4 background, leading to bispecific Ab (BsAbs) with a more rigid or flexible structure. All four Abs produced bound with good specificity and affinity to CD5 and HLA-DR present either on the same target or on different cells. Indeed, the BsAbs were able to efficiently redirect killing of HLA-DR+ leukemic cells by human CD5+ cytokine-induced killer T cells. Finally, all BsAbs had a functional Fc, as shown by their capacity to activate human complement and NK cells and to mediate phagocytosis. CD5xDR-CR3 was chosen as the best format because it had overall the highest functional activity and was very stable in vitro in both neutral buffer and in serum. In vivo, CD5xDR-CR3 was shown to have significant therapeutic activity in a xenograft model of human leukemia.

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“…Therefore, the Asn297 glycosylation does not affect significantly the half-life of the antibody in vivo. 35 Finally, C1q binding and CDC may be affected by the glycosylation pattern of IgG1 antibodies, but is not significantly modified by defucosylation [38][39][40] Rituximab PK Doses and routes of administration. RTX is usually administered by intravenous (i.v.)…”

Section: -34mentioning

confidence: 99%