geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Charge heterogeneity: Basic antibody charge variants with increased binding to Fc receptors


, : Charge heterogeneity: Basic antibody charge variants with increased binding to Fc receptors. Mabs 8(8): 1548-1560

NlmCategory="UNASSIGNED">We identified active isoforms of the chimeric anti-GD2 antibody, ch14.18, a recombinant antibody produced in Chinese hamster ovary cells, which is already used in clinical trials. 1,2,3 We separated the antibody by high resolution ion-exchange chromatography with linear pH gradient elution into acidic, main and basic charge variants on a preparative scale yielding enough material for an in-depth study of the sources and the effects of microheterogeneity. The binding affinity of the charge variants toward the antigen and various cell surface receptors was studied by Biacore. Effector functions were evaluated using cellular assays for antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. Basic charge variants showed increased binding to cell surface receptor FcγRIIIa, which plays a major role in regulating effector functions. Furthermore, increased binding of the basic fractions to the neonatal receptor was observed. As this receptor mediates the prolonged half-life of IgG in human serum, this data may well hint at an increased serum half-life of these basic variants compared to their more acidic counterparts. Different glycoform patterns, C-terminal lysine clipping and N-terminal pyroglutamate formation were identified as the main structural sources for the observed isoform pattern. Potential differences in structural stability between individual charge variant fractions by nano differential scanning calorimetry could not been detected. Our in-vitro data suggests that the connection between microheterogeneity and the biological activity of recombinant antibody therapeutics deserves more attention than commonly accepted.

US$19.90

PMID: 27559765

DOI: 10.1080/19420862.2016.1225642


Other references

Gaspar, F.W.; Harley, K.G.; Kogut, K.; Chevrier, J.; Mora, A.Maria.; Sjödin, A.; Eskenazi, B., 2016: Prenatal DDT and DDE exposure and child IQ in the CHAMACOS cohort. Although banned in most countries, dichlorodiphenyl-trichloroethane (DDT) continues to be used for vector control in some malaria endemic areas. Previous findings from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMAC...

Nummi, M.; Niku-Paavola, M.L.; Lappalainen, A.; Enari, T.M.; Raunio, V., 1983: Cellobio hydrolase ec 3.2.1.91 from trichoderma reesei. A 1,4-.beta.-D-glucan cellobiohydrolase was purified from the culture liquid of T. reesei by using biospecific sorption on amorphous cellulose and immunoaffinity chromatography. A single protein band in polyacrylamide-gel electrophoresis and 1 arc...

Toth, T.; Bartfai, J., 1960: Antihypertensive endocrine function of the kidney. Orvosi Hetilap 101: 1344-1346

Berger-Roochvarg, L.R., 1988: Pharmacologic issues in adolescence. Maryland Medical Journal 37(12): 959-961

Moukhwas, D.; Perrot, C., 1978: A new device for research on visual perception: the liquid crystals tachistoscope. As an alternative to occultation by a mechanical shutter or iris, tachistoscopic presentation can be achieved by transitory opacity of goggles, obtained via diffusion of liquid crystals. Light transmission through the goggles is a function of curr...

Aertgeerts, J.; Aussems, J.; Put, H., 1976: Double-blind investigation of two corticoid preparations for the treatment of eczematous skin disorders. Short communication. In a double blind fully randomised trial, three Belgian dermatologists independently treated 81 patients suffering from various eczematous skin disorders. After four weeks both the dermatologists and their patients assessed the results of a twice-...

Drain, P.K.; Holmes, K.K.; Hughes, J.P.; Koutsky, L.A., 2002: Determinants of cervical cancer rates in developing countries. Although cervical cancer (CC) is a leading cause of cancer-related deaths in developing countries, incidence rates vary considerably, ranging from 3 to 61 per 105 females. Identifying determinants of high vs. low rates may suggest population-level...

Piasecki Stefan; Stemmerik Lars; Friderichsen Johan D.; Higgins A.K., 1994: Stratigraphy of the post-Caledonian sediments in the Germania Land area, North-east Greenland. Rapport - Gronlands Geologiske Undersogelse = Report - Geological Survey of Greenland Pages 177-184

Rogers, S., 1962: An approach to the selective chemotherapy of the Shope virus-induced rabbit papillomas. Abstract.

Dhir, A.; Chavda, V., 2016: Pre- and post-exposure talampanel (GYKI 53773) against kainic acid seizures in neonatal rats. AMPA receptors play an important role in the neurobiology of neonatal epilepsy. The present study evaluated the effect of talampanel, a potent and selective non-competitive antagonist of AMPA receptors, against kainic acid-induced continuous seizu...