56. Jahrestagung der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie

Vorsitz

The Er Blood Group System –  how the journey of discovery solved old mysteries and new cases

eingeladene Redner

Vortrag

Molecular Blood Group Testing in Poland

Prof. Dr.

Full immunohematological workup despite treatment with an anti-CD47 monoclonal antibody

Immunohematology

Background Magrolimab is a monoclonal antibody targeting CD47. As a checkpoint inhibitor, it blocks the "don't eat me" signal expressed by cancer cells to avoid macrophage mediated killing. As CD47 is highly expressed on the surface of red blood cells as well, this therapy interferes with immunohematological workup. MagroEx, a new diagnostic reagent, blocks this interference thus enabling full immunohematological workup despite treatment with Magrolimab.Methods Here, we present a case of a 74-year-old 80 kg male AML patient treated with a first course of Magrolimab in a clinical phase 3 study. Due to an expected need of packed red blood cells (pRBC), extended blood group typing and antibody screening were initiated prior to administration of study medication. Column agglutination technique (Bio-Rad) was utilized for standard serological testing as well as antibody screening and differentiation. During saturation with study medication, extended RBC antigen typing (Kell, Cellano) was performed in LISS/Coombs in addition to cold antibody (IgM) screening in saline.Results In indirect agglutination testing (IAT) utilizing standard MagroEx concentration no agglutination was observed in samples with low study medication titers. After maximum saturation with study medication, an alternative protocol employing higher MagroEx concentrations was required in order to inhibit the agglutinating effect mediated by the therapeutic antibody. This use of a larger amount of MagroEx resulted in complete inhibition of Magrolimab interference, even at maximal anti-CD47 levels. Thus, the exclusion of alloantibodies and the provision of compatible pRBC became possible. Subsequently the patient could be safely transfused even during Magrolimab therapy.Conclusion The anti-CD47 study medication impaired antibody screening as well as serological crossmatch right from the start of treatment. By applying MagroEx a reliable inhibition of Magrolimab was achieved, so that valid serological crossmatches and antibody screenings became possible. Prior to treatment, extended blood grouping and antibody screening should be initiated as early as possible, to maximize transfusion safety. Fortunately, AB0 blood group typing is possible until day 12 of treatment.Offenlegung Interessenkonflikt: R. B. is a shareholder of imusyn

Freier Vortrag

Prof. Dr. Dr.

Immunohematological test reagent for pre-analytical depletion of anti-CD47 antibody from patient plasma

Background CD47 is an immune checkpoint that promotes tumor cell evasion as a "don"t eat me" signal. Consequently, anti-functional antibodies against CD47 are being tested as immune checkpoint inhibitors in a variety of malignant indications. Since, besides tumor cells, erythrocytes also express CD47, these antibodies cause pan-agglutination in the indirect antiglobulin test (IAT) with most available test systems, thus interfering with antibody screening and differentiation.Methods Using lentiviral vectors, the murine suspension cell MEL was engineered to express CD47 at a density of approximately 700,000 molecules per cell. These cells will henceforth be referred to as &quot;Magrosorb&quot;. Patient plasma was spiked with the anti-CD47 antibody Magrolimab, then subjected to pre-incubation as indicated, subsequently co-incubated with test erythrocytes in LISS buffer on conventional gel agglutination cards. Shown left to right are untreated plasma, plasma treated with parental cells (not CD47-transduced) and Magrosorb cells. Negativity of the right-most plasma for anti-RBC immune antibodies is apparent (Figure 1).Results Human plasma spiked with Magrolimab, currently the leading candidate as clinical CD47 antagonist resulted in 4+ positive reactions during antibody screening on conventional gel agglutination cards. Incubation of 1x107 Magrosorb cells in 25 µl of Magrolimab-spiked plasma and subsequent removal of Magrosorb cells by centrifugation depleted Magrolimab, resulting in a cleanly negative antibody screening test. In selected spiked plasma from antibody patients, these blood group antibodies became readily specifically detectable. We also demonstrate the possibility to stabilize the cells in fixating buffers, providing the possibility of intermittent batch production and distribution of test cells.Conclusion Medicinal antibodies causing pan-agglutination of test erythrocytes and thus obscure diagnostics provide a novel challenge for immunohematology testing. High antigen expression on non-human cells allows specific depletion of these medicinal antibodies from patient plasma without interfering with underlying specific immune antibodies. The system provides a readily adaptable tool for other medicinal or immune antibodies.Offenlegung Interessenkonflikt: There is no conflict of interest.

MOA 15

Sektion Immunhämatologie und Immungenetik

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Sektion Immunhämatologie und Immungenetik

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