Anti Adeno-Associated Virus 2 (AAV) Antibody Profile in Ovarian Cancer Ascitic Fluid: Implications for AAV Intraperitoneal Gene Therapy

Abstract

Objective: Recombinant adeno-associated virus (rAAV) type 2 is a common vector used in gene therapy. However, the presence of anti-AAV2 neutralizing antibodies or other neutralizing factors can significantly limit effective transduction. Intraperitoneal gene therapy could enable local delivery of the target gene directly to ovarian cancer cells. Until now, there have been no reports on the presence of anti-AAV antibodies in ascitic fluid, which might limit the effectiveness of rAAV as a candidate vector for intraperitoneal gene therapy. Thus, the characterization of the preexisting neutralization antibodies in ascitic fluid will provide insight into successful intraperitoneal gene therapy. Methods: The study was conducted on 23 ascitic fluid samples obtained from women with stage 3 and 4 ovarian cancer. The samples were collected to determine the presence of anti-AAV antibodies with ELISA test and the presence of neutralizing antibodies with neutralizing assay. Results: Our results indicate that anti-rAAV antibodies are present in 70%, whereas neutralizing factors/antibodies are present in 78% of analyzed ascitic fluid samples. This correlation provides evidence for the presence of additional, different from antibodies, currently unknown factors in ascites, which are able to inhibit AAV2 infection in the absence of anti-AAV antibodies. Conclusion: The presence of neutralizing antibodies against rAAV or other neutralizing factors in ascitic fluid should be taken into account during intraperitoneal gene therapy, because they might limit effective intraperitoneal gene therapy with rAAV as a vector.