BOSTON — A team at Children’s Hospital of Philadelphia (CHOP) led by Rebecca Ahrens-Niklas, MD, PhD, and Lindsey George, MD, has described a case of a brain tumor linked to a rare integration of adeno-associated virus (AAV). George presented the work at the American Society of Gene and Cell Therapy (ASGCT) conference in a plenary talk selected as the “presidential abstract” by ASGCT president, Terry Flotte, MD. The study, “Neuroepithelial tumor with AAV integration after intracisternal magna vector delivery,” was published in the New England Journal of Medicine.
Over the past 25 years, approximately 6,000 patients have received AAV gene therapy, with no established long-term safety concerns reported. However, the case documented by George and colleagues suggests a need for increased vigilance regarding potential integration events. The investigation began with a 5-year-old boy suffering from severe MPS1 deficiency who underwent gene therapy at 13 months using an AAV9 vector. Two years later, a routine scan revealed a large tumor, identified as a PLAG1-driven neuroepithelial tumor, raising questions about the implications of AAV integration in oncogenesis.
The RNA sequencing of the tumor revealed a fusion of the AAV9 vector to the PLAG1 gene, indicating a possible link to tumorigenesis. While the patient has shown positive clinical outcomes post-surgery, George emphasized the necessity for the gene therapy community to monitor transduced tissues closely and consider using lower vector doses and tissue-specific promoters to mitigate risks associated with AAV integration.
Use the database as your supply chain compass →
