Chimeric oncolytic adenovirus to break away from neutralizing antibodies

Systemic administration of an oncolytic virus (OV) is an attractive approach to disseminated or inaccessible cancers. However, neutralizing antibodies (NAbs) against OVs pose a challenge, as they restrict OV effectiveness by eliminating the virus from the bloodstream.1 The role of NAbs in intratumoral OV therapy, however, is less clear. The significance of NAbs in intratumoral OV treatment of brain tumors is also understudied and remains unknown. In a clinical trial testing the oncolytic adenovirus (OAd) Delta-24-RGD (DNX-2401) for pediatric patients with diffuse intrinsic pontine glioma (DIPG), 6 patients with higher NAb titers presented a shorter survival (12.5 months) compared to 6 patients with lower titers (21.2 months) (Table 1).