Exploring AAV Immune Responses in Gene Therapy: Insights from ASGCT's Community Quick Take

Understanding how the immune system interacts with adeno-associated virus (AAV) gene therapy is necessary for improving patient outcomes. ASGCT’s latest Community Quick Take broke down insights from a recent ASGCT workshop, Class Considerations on Immunogenicity for AAV Gene Therapy Products. Catch up on the discussion below, then check out the complete patient-friendly overview on the ASGCT Patient Education site. 

Why Does the Immune System Matter in Gene Therapy? 

The immune system plays an important role in determining whether AAV-based gene therapy will be successful in a CGT recipient. Similarly with vaccines and viral infections, the body recognizes AAV as foreign and generates antibodies that often affect treatment eligibility, efficacy, and the possibility of receiving a future dose.  

Key Takeaways about AAV Immune Responses 

Patient Eligibility and Pre-Existing Immunity

• Antibody Levels: Patients must be screened for pre-existing antibodies against AAV before receiving treatment. Antibody thresholds vary by therapy; for example, Zolgensma has a strict threshold while Elevidys allows a higher limit, making more patients eligible.  

• Use of Another Vector: Switching to a different AAV vector doesn’t always bypass immunity, since the body may still recognize and respond to the new vector. 

Managing Immune Responses to AAV Gene Therapy 

• Dose Amount Matters: While lower doses (like liver-targeting therapies) can be managed with glucocorticoids, higher-dose treatments (like brain-targeting therapies) trigger rapid immune responses, requiring different strategies.  

• Immune Modulation (or Suppression) Strategies: Conditioning treatments are often used to temporarily block antibody production and allow the therapy to work. Different therapies use different immune suppression strategies based on factors like organ targeting and patient characteristics. Research is also exploring ways to selectively suppress AAV-specific immune responses without affecting general immunity. 

Long-Term Impact on Treatment Outcomes 

• Antibodies Are Persistent: Patients may remain antibody-positive 25 years after exposure, making redosing a big challenge.  

• Overcoming Immune Barriers: Researchers are developing ways to eliminate antibody-producing cells, modify AAV capsids to reduce detection, and tailor immune modulation strategies to individual patients. 

Watch the full Community Quick Take here and gain expert insights in 25 minutes. Complete our brief survey to share your thoughts on these discussions. 

Continue the Conversation

To learn more about gene and cell therapy research exploring immune responses to AAV, consider becoming an ASGCT member or attending an upcoming ASGCT event. Stay updated on all patient-related programming by subscribing to The Patient Press. For more information on CGT treatments and clinical trials, visit the ASGCT Patient Education site. 

Alexis is ASGCT's Advocacy Programs Manager.

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