Anti-RhD-Mediated Immunosuppression: Can Monoclonal Antibodies Imitate the Action of Polyclonal Antibodies?

Оловникова, Н. И.

doi:10.5772/28744

Cited by 3 publications

(5 citation statements)

References 113 publications

(102 reference statements)

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“…BRAD5lab-b was effective but when produced for clinical use fucosylation was elevated and this came with a lower efficacy. Surprisingly, most B mAb-Ds (including AB5 and JAC10) have minimal ADCC 20,50 perhaps because EBV immortalises immature circulating B cells synthesising highly fucosylated IgG whereas plasma cells secreting low fucosylated protective antibodies lack EBV receptors 51 . The high fucosylation of these B mAb-Ds is likely to explain their low ADCC.…”

Section: Discussionmentioning

confidence: 99%

“…All the trial protocols varied; details of methods, ethics approval and informed consent are given in the original papers cited in Tables 4 and 5. Autologous RBC clearance measured the extent of radioactivity remaining in blood of D-positive subjects after injection of their ex vivo 51 Cr labelled RBC coated with anti-D. Study periods were between 1 h and 6 days after injection. Allogeneic studies measured clearance of D-positive RBC (labelled with 51 Cr or detected by flow cytometry) injected into D-negative recipients before (simulating postnatal prophylaxis) or after (equivalent to antenatal prophylaxis) anti-D administration, with blood samples taken up to 7 days.…”

Section: Analysis Of Data From Previous Clinical Trials Of Rbc Clearamentioning

confidence: 99%

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Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy

Kumpel

Saldova

Koeleman

et al. 2020

Sci Rep

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Anti-D immunoglobulin (Anti-D Ig) prophylaxis prevents haemolytic disease of the fetus and newborn. Monoclonal IgG anti-Ds (mAb-Ds) would enable unlimited supplies but have differed in efficacy in fcγRIIIa-mediated ADCC assays and clinical trials. Structural variations of the oligosaccharide chains of mAb-Ds are hypothesised to be responsible. Quantitative data on 12 Fc-glycosylation features of 23 mAb-Ds (12 clones, 5 produced from multiple cell lines) and one blood donor-derived anti-D Ig were obtained by HPLC and mass spectrometry using 3 methods. Glycosylation of mAb-Ds from human B-lymphoblastoid cell lines (B) was similar to anti-D Ig although fucosylation varied, affecting ADcc activity. In vivo, two B mAb-Ds with 77-81% fucosylation cleared red cells and prevented D-immunisation but less effectively than anti-D Ig. High fucosylation (>89%) of mouse-human heterohybridoma (HH) and Chinese hamster ovary (CHO) mAb-Ds blocked ADCC and clearance. Rat YB2/0 mAb-Ds with <50% fucosylation mediated more efficient ADCC and clearance than anti-D Ig. Galactosylation of B mAb-Ds was 57-83% but 15-58% for rodent mAb-Ds. HH mAb-Ds had non-human sugars. These data reveal high galactosylation like anti-D Ig (>60%) together with lower fucosylation (<60%) as safe features of mAb-Ds for mediating rapid red cell clearance at low doses, to enable effective, inexpensive prophylaxis.

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Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Data From Previous Clinical Trials Of Rbc Clearamentioning

confidence: 99%

Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy

Kumpel

Saldova

Koeleman

et al. 2020

Sci Rep

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“…The clinical practice of passive immunization of Rhesus (Rh) negative pregnant women with anti-Rh immunoglobulin (IgG) for the prevention of sensitisation to the Rh (D) antigen began in the 1960s, when multiple studies reported about its effectiveness and possible mechanisms of action [1][2][3]. The most important sensitizing event for Rh-negative women occurs at the end of the pregnancy, with detachment of the placenta during delivery.…”

Section: Introductionmentioning

confidence: 99%

“…The most important sensitizing event for Rh-negative women occurs at the end of the pregnancy, with detachment of the placenta during delivery. Prophylaxis with anti-D IgG induces a strong immunosuppressive effect, although its exact mechanism is not fully understood [3,4]. The proposed mechanisms include accelerated clearance of Rhpositive cells, epitope masking, inhibition due to antibodies against FcγRIIB or anti-idiotype, inhibition of immature dendritic cells, and inhibition of B-cell clones specific for the Rh antigen.…”

Section: Introductionmentioning

confidence: 99%

“…The proposed mechanisms include accelerated clearance of Rhpositive cells, epitope masking, inhibition due to antibodies against FcγRIIB or anti-idiotype, inhibition of immature dendritic cells, and inhibition of B-cell clones specific for the Rh antigen. Accelerated destruction of Rh-positive red blood cells is the most widely accepted main mechanism of action [3,4]. The incidence of postpartum anti-D sensitization has reduced from 13-19 to 0.9-1.8% with postpartum immunoprophylaxis and further to 0.1-0.3% with addition of antenatal immunoprophylaxis [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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A Multicenter, Randomized, Open-Label Trial Comparing the Efficacy and Safety of Monoclonal Anti-Rh (D) Immunoglobulin with Polyclonal Anti-Rh (D) Immunoglobulin for the Prevention of Maternal Rh-Isoimmunization

Chauhan

Nandanwar

Ramaiah³

et al. 2019

J Obstet Gynecol India

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Objectives To compare the efficacy and safety of monoclonal anti-Rhesus (anti-D) immunoglobulin (IgG) with polyclonal anti-D IgG in the prevention of maternal Rh-isoimmunization. Methods This was a randomized, multicenter, open-label, comparative clinical trial conducted in the obstetric in-patient departments of nine tertiary care hospitals in India. 206 Rhesus (D)-negative women, not sensitized to Rh antigen, and delivering Rh positive babies, received postpartum intramuscular administration of monoclonal or polyclonal anti-D IgG. The main outcome measures were the proportion of subjects protected from Rh-isoimmunization, identified by a negative indirect Coombs test (ICT) result, at day 180 after anti-D IgG administration, and incidence of adverse events. Results 105 subjects were randomized to the monoclonal group and 101 to the polyclonal group. 94 from the monoclonal group had a negative ICT result and none had a positive ICT result at day 180, whereas 87 from the polyclonal group had a negative ICT result and one had a positive ICT result; the rest (11 and 13 subjects respectively) were lost to follow-up. A total of 5 adverse events were reported (3 in the monoclonal group and 2 in the polyclonal group); only one of these was serious. All the adverse events were judged to be unrelated to the interventional drug. None of the subjects in the monoclonal group developed immunogenic reaction to the monoclonal anti-D. Conclusion The efficacy and safety of the monoclonal preparation of anti-D was comparable to the polyclonal preparation of anti-D when used in the prevention of maternal Rh-isoimmunization. Trial registration Clinical Trial Registration Number: CTRI/2015/09/006172.

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Prophylaxis of rhesus-sensitization of pregnant women. Experience of anti-rhesus immunoglobulin Rhesogam® N using

2021

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Aim. Retrospective assessment of the efficiency and safety of the anti-rhesus Rh (D) immunoglobulin Rhesogam N in preventing isoimmunization in Rh-negative women during pregnancy. Materials and methods. An analysis of medical records of 196 Rh-negative patients who received anti-Rh immunoglobulin Rhesogam N in the period 20192021 was performed. The indications for the drug were the aspiration of chorionic villi, amniocentesis and prenatal prophylaxis in women with negative level of anti-Rh antibodies and in the case of Rh-positive husbands. Results. In total, 227 doses of the anti-rhesus immunoglobulin Rhesogam N were administered, including those women who underwent invasive procedures (aspiration of chorionic villi, amniocentesis). There were no adverse events, including anaphylaxis or drug-related events. 172 rhesus-positive babies were born. No cases of hemolityc disease of the newborns were reported. Anti-Rh antibodies were not found in their mothers after childbirth. Conclusion. The study confirmed the efficacy and safety of the antiresus Rh (D) immunoglobulin Rhesogam N for the prevention of Rh isoimmunization.

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Anti-RhD-Mediated Immunosuppression: Can Monoclonal Antibodies Imitate the Action of Polyclonal Antibodies?

Cited by 3 publications

References 113 publications

Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy

Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy

A Multicenter, Randomized, Open-Label Trial Comparing the Efficacy and Safety of Monoclonal Anti-Rh (D) Immunoglobulin with Polyclonal Anti-Rh (D) Immunoglobulin for the Prevention of Maternal Rh-Isoimmunization

Prophylaxis of rhesus-sensitization of pregnant women. Experience of anti-rhesus immunoglobulin Rhesogam® N using

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