A targeted immunotherapy using a specially designed fusion protein for the treatment of fetal and neonatal alloimmune thrombocytopenia (FNAIT) has shown promising results in animal models, according to a recently published abstract.
FNAIT affects pregnancies when a mother develops antibodies against paternally inherited platelet antigens in the fetus,most often HPA-1a.
These maternal alloantibodies cross the placenta and target fetal platelets, leading to severe thrombocytopenia (dangerously low platelet counts) and the risk of life-threatening bleeding, such as intracranial hemorrhage (ICH) in newborns.
Current therapies, like intravenous immunoglobulin (IVIG) or FcRn-blocking antibodies, work by broadly suppressing maternal immunity or by reducing the transfer of all antibodies to the fetus. While these can relieve symptoms, they are not selective—meaning they can have side effects due to global immune suppression and do not directly eliminate the disease-causing antibodies.
FNAIT remains a clinical challenge because available treatments do not address the root cause: the presence of specific pathogenic alloantibodies and the B cells that produce them.
In this context, researchers developed a targeted immunotherapy using a specially designed fusion protein. This chimeric protein features a murine single-chain fragment of β3 integrin that has been humanized to present the HPA-1a epitope, fused to the Fc region of mouse IgG2a.
The novel protein is engineered to neutralize and clear circulating anti-HPA-1a antibodies and eplete the specific B cells responsible for producing these antibodies. To evaluate its effectiveness, the authors expressed and purified both the humanized fusion protein (APLDQ-cβ3-E2-Fc) and a wild-type control protein, then tested their ability to bind anti-HPA-1a antibodies in laboratory and animal models.
Results showed that the APLDQ-cβ3-E2-Fc fusion protein selectively bound to multiple anti-HPA-1a monoclonal antibodies as well as polyclonal antisera from immunized mice. When introduced into mice previously immunized to generate HPA-1a antibodies, the fusion protein successfully reduced the concentration of these circulating alloantibodies.
Furthermore, in adoptive transfer experiments, where B and T cells from immunized mice were introduced into immunodeficient recipients,the addition of the fusion protein significantly attenuated the production of HPA-1a-specific antibodies after antigen challenge. This indicated that the therapy could directly target and reduce both existing pathogenic antibodies and the B cells responsible for their generation.
“This approach provides an antigen-specific, targeted alternative to traditional immunosuppressive therapies for FNAIT patients, with the potential for curative treatment. Future studies will focus on optimizing the therapeutic dose and timing, as well as evaluating the long-term efficacy in FNAIT mouse models,” the authors concluded.
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