Nicholas Giovannone, PhD, on the Potential Benefits of Redosing Gene Therapy

This is the second part of an interview with Nicholas Giovannone, PhD. For the first part, click here.

“Our hope broadly is that this can expand treatment options for patients and improve overall for the field the efficacy of gene therapies and durability of gene therapies.”

Nicholas Giovannone, PhD, a senior principal scientist at Regeneron, gave a presentation at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2024, in New Orleans, LA, on a novel strategy that uses bispecific antibodies to suppress an immune response to an adeno-associated virus (AAV) vector in order to allow for AAV redosing. The strategy was successfully tested in nonhuman primates and compared favorably to a more traditional strategy using rituximab.

After discussing the details of this research with CGTLive® at the conference, Giovannone spoke about the reasons why AAV redosing is important. He pointed out that although AAV is ideally a one-time treatment, its effectiveness can decline because of several factors. First, a loss of the AAV genome may occur as target organs like the liver grow or its cells divide. Second, cytotoxic T-cells can destroy transduced cells, also reducing efficacy over time. Third, patients may eventually want a second AAV vector-based therapy in the future—either because an improved product becomes available or as a treatment for another condition—but currently long-lived neutralizing antibodies limit this possibility.

Giovannone also discussed the problem of preexisting immunity caused by natural exposure to AAVs. He pointed out that this type of preexisting immunity actually needs to be addressed in a different manner than the immunity from previous AAV vector-based treatment, and noted that his lab has been working on this problem as well and covered their work in a presentation at ASGCT’s meeting last year. Giovannone also highlighted the collaborative nature of the work and the importance of events like ASGCT in fostering innovation and shared progress in the field.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.

REFERENCE
1. Giovannone N. Successful AAV vector re-administration via two distinct B cell immunomodulation strategies in non-human primates. Presented at: at ASGCT 28th Annual Meeting, held May 13 to 17, 2024, in New Orleans, LA.