Safety Findings of Dosing Gene Therapy Vectors in NHP With Pre-existing or Treatment-Emergent Anti-capsid Antibodies

We present safety findings from two 12-week studies in nonhuman primates (NHPs) with pre-existing or treatment-emergent antibodies. In the first study, NHPs with varying levels of naturally acquired anti-AAV5 antibodies were dosed with an AAV5-based vector encoding human factor VIII (hFVIII). In the second study, NHPs with no pre-existing anti-AAV antibodies were dosed with an AAV5-based vector carrying the beta subunit of choriogonadotropic hormone (bCG); this led to the induction of high-titer antibodies against the AAV5 capsid. Four weeks later, the same NHPs received an equivalent dose of an AAV5-based vector carrying human factor IX (hFIX). In both of these studies, the administration of vectors carrying hFVIII, bCG, and hFIX was well-tolerated in NHPs with no adverse clinical pathology or microscopic findings. These two studies demonstrate the safety of AAV-based vector administration in NHPs with either low-titer pre-existing anti-AAV5 antibodies or re-administration, even in the presence of high-titer antibodies.PMID:37921115 | DOI:10.1177/01926233231202995

Source: Toxicologic Pathology - November 3, 2023 Category: Pathology Authors: Sundeep Chandra Brian R Long Carlos Fonck Andrew C Melton Jeremy Arens Jill Woloszynek Charles A O'Neill Source Type: research