Vectorized Human Antibody-Mediated Anti-Eosinophil Gene Therapy
Maria Gioulvanidou1, Selenay Sarklioglu1, Xinlei Chen2
1Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
Human Gene Therapy
|December 26, 2024
Summary
Gene therapy using adeno-associated virus (AAV) delivered a novel antibody to target eosinophils. This approach shows potential for a one-time treatment to suppress eosinophil levels in chronic hypereosinophilia.
Area of Science:
- Hematology
- Immunology
- Gene Therapy
Background:
- Chronic hypereosinophilia involves elevated eosinophils, leading to organ damage.
- Current therapies for hypereosinophilia have limited efficacy and significant side effects.
Purpose of the Study:
- To develop a novel, one-time gene therapy for chronic hypereosinophilia.
- To evaluate adeno-associated virus (AAV)-mediated delivery of an anti-human eosinophil antibody.
Main Methods:
- Generated a human monoclonal antibody (mAb) targeting Siglec8 on eosinophils.
- Created an AAV vector (AAVrh.10hAntiEos) expressing the anti-eosinophil antibody.
- Administered the AAV vector to mouse models to assess efficacy and safety.
Main Results:
- AAVrh.10hAntiEos successfully produced the anti-eosinophil antibody in vivo.
- The antibody effectively bound to eosinophils, induced apoptosis, and mediated antibody-dependent cellular cytotoxicity.
- Gene therapy suppressed human eosinophil levels in immunodeficient mice.
Conclusions:
- AAV-mediated delivery of an anti-Siglec8 antibody is a promising strategy for chronic hypereosinophilia.
- This novel gene therapy approach has the potential for a safe and effective one-time treatment.
- Further development of AAVrh.10hAntiEos could offer therapeutic benefits for patients.
