Correlation between adenovirus-neutralizing antibody titer and adenovirus vector-mediated transduction efficiency following intratumoral injection

摘要

Pre-existing anti-adenovirus neutralizing antibodies (AdNAbs) are a major barrier in clinical gene therapy using adenovirus vectors; however, the transduction profile of adenovirus vectors in the presence of AdNAbs following intratumoral injection has not been fully examined, although such vectors are often intratumorally injected in clinical studies. In this study, we evaluated the correlation between the titer of AdNAbs in the serum and the transduction profiles in the tumor and the liver following intratumoral administration into mice possessing various titers of AdNAbs. Adenovirus vector-mediated transduction in the tumor was inhibited by AdNAbs; however, when the titer of AdNAbs was less than 200, the levels of inhibition in the transduction efficiencies within the tumor ranged from approximately 2- to 100-fold. A more than 2500-fold reduction of adenovirus vector-mediated transduction was found in most of the mice when the titers of AdNAbs were >200. On the other hand, the transduction efficiencies in the liver were largely reduced almost to the levels of the mock-transduced mice even at the low titers of AdNAbs. These results provide crucial information for the clinical use of adenovirus vectors.