In a recent study, Rallybio’s anti human platelet antigen (HPA)-1a antibody RLYB212 successfully prevented fetal and neonatal alloimmune thrombocytopenia (FNAIT) in mice, according to an abstract that will be presented at the American Society of Hematology Annual Meeting and Exposition.
The study used female mice bred with male mice that only expressed the HPA1a gene. The idea was to simulate the human context in which FNAIT occurs, with the mother producing antibodies directed against paternity-inherited platelet antigens.
Pregnant mice received RLYB212 injections at two doses and then a transfusion of HPA1a platelets meant to induce alloimmunization. A control group of mice received the transfusion but no RLYB212.
Results showed that RLYB212 at both doses successfully prevented alloimmunization and FNAIT, as all mice born to mothers receiving the drug were born healthy and with normal platelet counts. The mother of the mice did not experience any significant adverse effects after RLYB212 administration.
“Taken together, these data establish that prophylactic administration of the HPA-1a-specific antibody RLYB212 to pregnant mice is both effective and safe in preventing maternal alloimmunization and FNAIT,” the authors wrote. “ These preclinical findings further support the potential of RLYB212 as a prophylactic therapy, paving the way for human studies aimed at preventing FNAIT in pregnant women,”
About anti-HPAa1 antibodies and FNAIT
FNAIT occurs because maternal antibodies targeting the HPAa1 in fetal platelets cross the placenta, binding to their targets and inducing an immune reaction that leads to platelet destruction. Furthermore, this immune reaction can impair fetal platelet production and cause placental dysfunction.
There is growing interest in the potential of anti-HPAa1 antibodies in FNAIT prevention. Their theoretical mechanism of action consists of clearing HPAa1 platelets before they are recognized by the maternal immune system, thus preventing the production of harmful antibodies.
In cases where immunization has already occurred, some anti-HPAa1 antibodies could bind to fetal platelets, preventing the binding of maternal antibodies without unleashing a harmful immune response.
