Abstract LB-188: Breast cancer immunotherapy using magnetized HSV1716

Background: Oncolytic viruses (OV) are encouraging new immunotherapies for cancer. OVs, replicate in cancer cells inducing immunogenic cell death (ICD) and activating antitumor immunity. To date, clinical use has focused on intratumoral delivery due to concerns over inadequate tumor targeting following systemic administration. We hypothesize that magnetizing OVs and magnetic guidance strategies will improve systemic delivery by protecting the viruses from inactivating immune mechanisms and non-specific adsorption. Methods: To investigate this, we synthesized and characterized complexes of magnetized oncolytic herpes simplex virus (HSV1716) co-assembled with biocompatible magnetic nanoparticles (MAG) derived from magnetotactic bacteria (AMB-1) to give MAG-HSV1716 complexes. Characterization of the physical, chemical and oncolytic potential of our MAG-HSV1716 was performed. The safety and efficacy of our nanomedicine in combination with magnetic guidance strategies were also assessed in vivo. Results: Stable MAG-HSV1716 complexes of ~160nm diameter successfully infected human and murine breast cancer cells in a dose-dependent manner, and induced tumor oncolysis. Following MAG-HSV1716 infection a significant increase in viral replication (ICP0, gB, ICP8), ICD (HMGB1, CALR, ATP) and apoptotic (CASP 3, CASP8, FASL) signals were detected. Intravenous delivery of MAG-HSV1716 resulted in reduced tumour burden in the presence of magnetic guidance (MAG-HSV1716 448.3mm³ vs. HSV1716 670.6mm³; p ≤ 0.05, n=6-9 mice/group) and an increase in tumor-infiltrating T-cells, NK cells and neutrophils. Furthermore, MAG-HSV1716 were protective in the presence of neutralizing Abs both in vitro and in vivo. Conclusion: This study indicates that magnetizing HSV1716 results in viral protection from neutralizing antibodies and in combination with magnetic guidance reduces tumor burden and induces anti-tumor immunity. Citation Format: Haider AL-Janabi, Joe Conner, Faith Howard, Stuart Hunt, Zainab Taher, Sarah Staniland, Munitta Muthana. Breast cancer immunotherapy using magnetized HSV1716 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-188.