Clearance of Rh D-positive red cells with monoclonal anti-D

Thomson, Amanda; Contreras, Marcela; Teesdale, Phyllis; Mollison, P. L.; Gorick, B.D.; Hughes‐Jones, N. C.; Kumpel, Belinda M.; Chapman, G. E.; Lane, R. S.

doi:10.1016/0140-6736(90)92767-c

Cited by 65 publications

(56 citation statements)

References 8 publications

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“…The concurrent appearance of 51 Cr in plasma (Figure 3) with no re-emergence of IgG1-coated cells suggests total cell clearance and destruction. The degree of clearance seen was greater than in the previous study of Fog-1, 27 despite comparable levels of coating in some subjects and similar levels of elution from the D antigen (31%/h in vitro, data not shown). The ability of our Fog-G1 to promote faster and more complete hemolysis than in the earlier study may be due to the different expression system used here.…”

Section: Discussioncontrasting

confidence: 46%

“…There is extensive accumulated evidence over several decades of administering anti-D antibodies to humans, and the original Fog-1 was assessed in volunteers for its suitability in HDN prophylaxis. 27 Unexpectedly, 2 of our subjects had mild febrile reactions coincidental with the appearance of radiolabel in the plasma, suggesting a response to the destructive process. The previous study of active Fog-1 reported no reactions, 27 but the volumes of coated cells were nearly 20 times lower than injected here.…”

Section: Discussionmentioning

confidence: 99%

“…27 Unexpectedly, 2 of our subjects had mild febrile reactions coincidental with the appearance of radiolabel in the plasma, suggesting a response to the destructive process. The previous study of active Fog-1 reported no reactions, 27 but the volumes of coated cells were nearly 20 times lower than injected here. Since the 2 febrile subjects had both wild-type and modified antibody, it is not possible to attribute the reactions to either one.…”

Section: Discussionmentioning

confidence: 99%

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Intravascular survival of red cells coated with a mutated human anti-D antibody engineered to lack destructive activity

Armour

Parry-Jones

Beharry

et al. 2006

Blood

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Section: Discussioncontrasting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Intravascular survival of red cells coated with a mutated human anti-D antibody engineered to lack destructive activity

Armour

Parry-Jones

Beharry

et al. 2006

Blood

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“…The putative synergy would certainly be more easily detected by using a lower dose of each monoclonal anti-D selected in a range in which the clearance rate would be expected to be proportional to the injected amount (eg, 0.5 g) as suggested by the dose-response effect observed with 26C1. Concerning the effect of blending, it should be pointed out that our results are in agreement with 2 previous studies done in humans 33 and in chimpanzees 34 in which no synergy between 2 anti-D was observed.…”

Section: Discussionsupporting

confidence: 82%

Functional in vivo characterization of human monoclonal anti-D in NOD-scid mice

Bazin

Aubin

Boyer

et al. 2002

Blood

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IntroductionHuman monoclonal antibodies of various specificities can now be prepared by using cellular or molecular technologies. Several of these antibodies could have interesting therapeutic applications, such as human monoclonal anti-D that could be used to replace plasma-derived polyclonal antibodies for the prevention of the hemolytic disease of the newborn. 1 Contrary to plasma-derived anti-D preparations that rely on the availability of immunized donors, monoclonal anti-D prepared by culture of immortalized cell lines give access to an unlimited supply of standardized preparations. However, as is the case for other antibody specificities, the selection of the most appropriate monoclonal anti-D for therapeutic use represents a significant challenge.The mechanism by which anti-Ds suppress Rh D immunization is still unclear. Some of the proposed mechanisms rely on the interaction between the Fc portion of anti-D and different Fc␥ receptors (Fc␥R) and could lead either to the inhibition of antigen-specific B cells by the binding of antigen-antibody complexes or to the rapid clearance and destruction of the Rh D ϩ red blood cells (RBCs) coated with anti-D. 2 These 2 mechanisms are not mutually exclusive, and both require the efficient binding of the antibodies to the Rh D ϩ RBCs in vivo. However, work with Fc␥R-deficient mice suggested that immune suppression could occur by antigenic epitope masking and thus be independent of the Fc portion of immunoglobulin G (IgG). 3 Although the mechanism of inhibition of immune response is still unresolved, it is likely that the anti-D preparations suitable for the prevention of the hemolytic disease of the newborn will be among those exhibiting the most efficient antigen binding in vivo.Because of obvious ethical problems in studying Rh D ϩ RBC destruction in Rh D Ϫ individuals, the biologic activity of monoclonal anti-D has been evaluated mainly by using in vitro tests intended to reproduce the processes involved in antibodydependent in vivo RBC destruction. Clearance of RBCs coated with antibodies may depend to a large extent on the interaction of antibodies with the Fc␥Rs present on macrophages in the spleen. 4 However, because splenic macrophages are difficult to obtain, only indirect assessment of antibody-Fc␥R interactions can be done in vitro by using natural killer cells to measure Fc␥RIII-mediated interactions 5,6 and monocytes to measure Fc␥RI/II-mediated interactions. 7,8 One of the main problems associated with in vitro tests is that the results of these assays will vary, depending on a number of parameters that are likely to differ from the in vivo situation (eg, RBC-phagocyte ratio, degree of RBC sensitization, etc). Thus, the suitability of these in vitro assays to predict the ability of monoclonal anti-D to prevent Rh D alloimmunization has not been demonstrated. 9,10 In the past 10 years, the isolation of immunodeficient mouse strains has opened new possibilities for the early in vivo testing of human proteins and cells. The nonobese diabetic/severe combi...

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“…Study of immunosuppressive properties of monoclonal and recombinant anti-D antibodies was carried out following evaluations of their safety, pharmacokinetics, as well as the ability to accelerate the clearance of sensitized red cells (Thomson et al, 1990;Blancher et al, 1993;Goodrick et al, 1994;Bichler et al, 2004). To date, over ten anti-D IgG1 and two IgG3 of different origin (lymphoblastoid cell lines, human-mouse heterohybridomas, CHO, YB2/0) have been tested on volunteers.…”

Section: What In Vivo Investigations Of Monoclonal and Recombinant Anmentioning

confidence: 99%

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

Оловникова¹

2012

Immunosuppression - Role in Health and Diseases

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Clearance of Rh D-positive red cells with monoclonal anti-D

Cited by 65 publications

References 8 publications

Intravascular survival of red cells coated with a mutated human anti-D antibody engineered to lack destructive activity

Intravascular survival of red cells coated with a mutated human anti-D antibody engineered to lack destructive activity

Functional in vivo characterization of human monoclonal anti-D in NOD-scid mice

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

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