Scientific Publications Database

Article Title: Molecular retargeting of antibodies converts immune defense against oncolytic viruses into cancer immunotherapy
Authors: Niemann, Julia; Woller, Norman; Brooks, Jennifer; Fleischmann-Mundt, Bettina; Martin, Nikolas T.; Kloos, Arnold; Knocker, Sarah; Ernst, Amanda M.; Manns, Michael P.; Kubicka, Stefan; Wirth, Thomas C.; Gerardy-Schahn, Rita; Kuehnel, Florian
Journal: NATURE COMMUNICATIONS Volume 10
Date of Publication:2019
Abstract:
Virus-neutralizing antibodies are a severe obstacle in oncolytic virotherapy. Here, we present a strategy to convert this unfavorable immune response into an anticancer immunotherapy via molecular retargeting. Application of a bifunctional adapter harboring a tumor-specific ligand and the adenovirus hexon domain DE1 for engaging antiadenoviral antibodies, attenuates tumor growth and prolongs survival in adenovirus-immunized mice. The therapeutic benefit achieved by tumor retargeting of antiviral antibodies is largely due to NK cell-mediated triggering of tumor-directed CD8 T-cells. We further demonstrate that antibody-retargeting (Ab-retargeting) is a feasible method to sensitize tumors to PD-1 immune checkpoint blockade. In therapeutic settings, Ab-retargeting greatly improves the outcome of intratumor application of an oncolytic adenovirus and facilitates long-term survival in treated animals when combined with PD-1 checkpoint inhibition. Tumor-directed retargeting of preexisting or virotherapy-induced antiviral antibodies therefore represents a promising strategy to fully exploit the immunotherapeutic potential of oncolytic virotherapy and checkpoint inhibition.