Passive Perinatal Immunotherapy via Transamniotic Antibody Delivery

A non-invasive method that reduces the risk of alloimmune disorders and neurological complications

Background

Limitations in the placental transfer of antibodies from the mother to the fetus can render the fetus vulnerable to a range of serious infections. Administration of therapeutic antibodies after birth may be ineffective because the disease is already too advanced at birth. Administration of antibodies to the fetus, on the other hand, can substantially reduce the risk of infection. For example, it has been shown to be effective against congenital cytomegalovirus (CMV) infection, which is the leading cause of congenital disabilities such as neurological, cognitive, and auditory impairments. However, there are no safe and effective methods for transferring antibodies to the fetus. Indirect delivery via trans-venous injection to the mother may require multiple injections, is limited by selective placental transfer, and the amount reaching the fetus cannot be measured or verified. Direct delivery to the fetus, on the other hand, is invasive and may result in severe complications. 

Technology Overview

 This invention is an effective and safe method for delivering therapeutic antibodies to the fetus. The new method uses the amniotic cavity/fluid as the route of administration. Amniotic fluid/cavity has previously been used for the administration of fetal stem cells. The inventors show that the same mechanism can be employed for effective administration of therapeutic antibodies to the fetus. This invention has the potential to enhance passive fetal immunotherapy.

The inventors delivered different concentrations of human IgG to pregnant rodents via intra-amniotic injection. They assessed the presence and concentration of IgG in the serum, bone marrow, spleen, thymus, and brain at term. Compared to saline-injected controls, they detected significant concentrations of human IgG in the serum, bone marrow, spleen, thymus, and brains of all fetuses for all injection concentrations. The results of these experiments suggest that transamniotic fetal immunotherapy is an effective method for perinatal management of certain infectious diseases. 

Further Detail

Whitlock, A.E., Labuz, D.F., Kycia, I., Zurakowski, D., Fauza, D.O., 2021. Passive perinatal immunotherapy via transamniotic antibody delivery. Journal of Pediatric Surgery.

Benefits

• Reduces the risk of alloimmune disorders and infections at the prenatal stage
• Reduces the risk of neurological complications associated with infectious diseases
• Improves the transfer of antibodies for which placental transfer does not work, such as IgA, IgD, and IgE
• The effect of antibodies administered via amniotic cavity/fluid can last well into the neonatal period
• Non-invasive

Applications

• Prevention of infections such as CMV, toxoplasmosis, rubella, herpes virus, and HIV, at the prenatal stage
• Treatment of autoimmune hemolytic disorders in the fetus
• Reducing the burden of surgical diseases 

IP Status

• Patent application submitted