Abstract
G47Δ is a triple-mutated oncolytic herpes simplex virus type 1 designed to induce antitumor immune responses efficiently. We examine the usefulness of G47Δ 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 G47Δ 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 G47Δ+RFA treatment caused smaller volumes of right tumors, accompanied by increased CD8(+)/CD45(+) T cells, compared with G47Δ monotherapy. After depletion of CD8(+) T cells, the enhanced efficacy on the contralateral tumors was completely abolished. Neoadjuvant G47Δ 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 G47Δ effectively enhances the efficacy of RFA via CD8(+) T cell-dependent immunity that is further augmented by an immune checkpoint inhibitor.