OA4-AM24-ST-19 - Evaluating the Influence of IMC-002, a Novel Anti-CD47 Monoclonal Antibody, on Pretransfusion Compatibility Testing

CD47, a widely expressed transmembrane protein in human cells, has emerged as a prominent target for cancer immunotherapy. Given its presence on both red blood cells (RBCs) and cancer cells, CD47-targeting agents utilized in previous clinical trials have been shown to significantly interfere with pretransfusion compatibility testing. Moreover, the characteristics of interference have varied among different drugs. This study aims to assess the effects of IMC-002, a novel anti-CD47 monoclonal antibody, on pretransfusion compatibility testing.

Study

Design/Methods:

Group O/RhD+, AB/RhD+, A/RhD- and AB/RhD− whole blood was pre-incubated with IMC-002 at concentrations of 500, 1000, and 2000 μg/mL for 30 minutes at 37°C. ABO/RhD typing was performed using the tube method, gel cards, and an automated analyzer, Qwalys3 (Diagast, Loos, France). Direct antiglobulin test (DAT) was conducted using gel cards. Extended blood group antigen testing was carried out by the tube method. Antibody screening tests were performed using both the tube method and gel cards on unexpected antibody-free AB/RhD+ plasma, to which IMC-002 was added at various concentrations (0.1, 1, 10, 100, 500, 1000, and 2000 μg/mL). The binding of IMC-002 to RBCs was evaluated using flow cytometry.

Results/Findings: False-positive results (4+) for ABO forward typing and RhD typing were observed using Qwalys3. Conversely, false-positive results in ABO reverse typing (±) using Qwalys3 were seldom observed. The tube method yielded false-positive results (ranging from ± to 3+) for ABO forward, ABO reverse, and RhD typing. However, this interference could be mitigated by washing the RBCs prior to forward typing and by applying saline replacement during reverse typing. Using gel cards, false-positive results for ABO reverse typing were noted (3+mf), but no false-positives were observed in ABO forward typing or RhD typing. DAT demonstrated weak false positive results (±). Extended blood group antigen testing with washed RBCs showed no interference. Antibody screening tests using plasma spiked with IMC-002 exhibited panreactivity in a concentration-dependent manner, both in the tube method and on gel cards. Finally, flow cytometry revealed no or minimal binding of IMC-002 to RBCs (Figure A).

Conclusions:

IMC-002 induced interference during ABO/RhD typing which could be mitigated by using washed RBCs and saline replacement. Plasma spiked with IMC-002 showed concentration-dependent panreactive results in antibody screening tests. However, it is presumed that these interferences are caused by mechanisms other than typical antigen-antibody reactions. Further research is required to elucidate this phenomenon.