Neoadjuvant Use of Oncolytic Herpes Virus G47? Enhances the Antitumor Efficacy of Radiofrequency Ablation

ABSTRACT: G47? is a triple-mutated oncolytic herpes simplex virus type 1 designed to induce antitumor immune responses efficiently. We examine the usefulness of G47? as a neoadjuvant therapy for radiofrequency ablation (RFA), a standard local treatment for certain cancers such as liver cancer, but remote recurrences within the same organ often occur. In A/J mice harboring bilateral subcutaneous Neuro2a tumors, the left tumors were treated with G47? intratumoral injections followed by RFA. Whereas the RFA-treated tumors were all eradicated, the growth of the right tumors was evaluated and tumor-infiltrating lymphocytes were analyzed. The G47?+RFA treatment caused smaller volumes of right tumors, accompanied by increased CD8+/CD45+ T cells, compared with G47? monotherapy. After depletion of CD8+ T cells, the enhanced efficacy on the contralateral tumors was completely abolished. Neoadjuvant G47? led to rejection of rechallenged tumors, which was caused by efficient induction of specific antitumor immune responses shown by enzyme-linked immunospot (ELISPOT) assays. Treatment of tumor-harboring animals with an anti-programmed cell death 1 ligand 1 (PD-L1) antibody led to even greater efficacy on contralateral tumors. Our study indicates that the neoadjuvant use of G47? effectively enhances the efficacy of RFA via CD8+ T cell-dependent immunity that is further augmented by an immune checkpoint inhibitor. Graphical Abstract Radiofrequency ablation (RFA) is an effective local treatment, but remote recurrences often occur. In immunocompetent mice harboring bilateral subcutaneous tumors, treatment with oncolytic herpes G47? prior to RFA causes enhanced efficacy on remote tumors with increased immune responses, further boosted by following with anti-PD-L1 antibody. Such sequential treatments should be useful.

SUBMITTER: Yamada T 

PROVIDER: S-EPMC7501409 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature