ABSTRACT
Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary complex-type oligosaccharide attached to Asn297 of the Fc is essential for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that generate structural heterogeneity (glycoforms) exhibit unique biological activities. Hence, efficient and quantitative glycan analysis techniques have been increasingly important for the development and quality control of therapeutic antibodies, and glycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosylation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibilities for the design of novel antibody therapeutics. Furthermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosynthases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next-generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety, functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.
Subject(s)
Animals , Humans , Antibodies, Monoclonal , Pharmacokinetics , Therapeutic Uses , Glycosylation , Immunoglobulin G , Chemistry , Metabolism , Protein Engineering , Methods , Receptors, Fc , Chemistry , Metabolism , Treatment OutcomeABSTRACT
To investigate whether magnesium abnormalities are associated with the administration of magnesium-containing laxatives in a palliative care setting, we measured the serum magnesium levels in 48 patients with advanced cancer at our palliative care unit (PCU). The mean magnesium concentration in all patients was 2.09 mg/dl (confidence interval [CI], 1.38-3.62). Patients receiving magnesium-containing laxatives (n=38) showed significantly higher serum magnesium concentrations than patients without laxatives (n=10) (2.17 mg/dl vs 1.8 mg/dl, p=0.006). Although 10 patients had serum magnesium abnormalities (hypomagnesemia, 8 and hypermagnesemia, 2), we did not observe clinical manifestation associated with magnesium abnormalities. Interestingly, neither the duration nor the dose of laxatives correlated with serum magnesium concentration. Overall, patients at the PCU tend to have magnesium abnormalities and their symptoms may be analogous to those of advanced cancer patients; in particular, terminal patients with such symptoms might be considered to have magnesium abnormalities.
ABSTRACT
A man in his 60s, who was diagnosed as having postoperative recurrent gastric cancer with lymph node and spinal metastases, was admitted to our palliative care unit (PCU). He was unable to receive further aggressive chemotherapy for cancer because of bilateral hydronephrosis and chronic renal failure. He had chronic urethral infection and hence required continuous antibiotic administration. Although his infection was well controlled with antibiotics, his oral intake gradually declined. Seventeen days after admission, he developed systemic hemorrhage, including hematuria and oral bleeding. Coagulation tests revealed that the patient had markedly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) but no thrombocytopenia, fibrinogen consumption, or increased fibrin/fibrinogen degradation products (FDP) level. Serum level of protein induced by vitamin K absence or antagonist II (PIVKA-II) was markedly high, and vitamin K level was below the lower limit of the reference range. After he was administered intravenous vitamin K, his symptoms markedly improved. Many patients with advanced cancers tend to have malnutrition, anorexia, and chronic infection that require antibiotic administration. Prophylactic administration of vitamin K might be sometimes necessary for preventing catastrophic hemorrhage.