Potential role for oral tolerance in gene therapy

Area of Science:

• Immunology
• Gene Therapy
• Autoimmune Diseases

Background:

• Oral immunotherapies aim to induce antigen-specific immune tolerance for autoimmune diseases and allergies.
• Anti-drug antibody formation is a challenge in protein replacement therapies, such as for hemophilia.

Purpose of the Study:

• To investigate if oral delivery of bioencapsulated antigens can prevent immune responses against therapeutic transgene products in gene therapy.
• To assess the efficacy of this approach in a hemophilia A mouse model.

Main Methods:

• Utilizing transplastomic lettuce cells to bioencapsulate coagulation factor antigens for oral delivery.
• Administering repeated oral doses of these bioencapsulated antigens to hemophilia A mice.
• Treating mice with adeno-associated viral gene transfer for factor VIII expression.

Main Results:

• The oral immunotherapy approach significantly reduced antibody development against factor VIII in treated hemophilia A mice.
• This method demonstrated a substantial decrease in inhibitor formation compared to controls.

Conclusions:

• The strategy of oral antigen delivery, using bioencapsulated antigens, can effectively prevent immune responses against therapeutic transgene products.
• This research supports the application of oral tolerance principles to enhance the safety and efficacy of gene therapy for inherited bleeding disorders and potentially other conditions.