Immune Checkpoint Blockade, Immunogenic Chemotherapy or IFN-α Blockade Boost the Local and Abscopal Effects of Oncolytic Virotherapy

Abstract

Athough the clinical efficacy of oncolytic viruses has been demonstrated for local treatment, the ability to induce immune-mediated regression of distant metastases is still poorly documented. We report here that the engineered oncolytic vaccinia virus VV WR

Tumor Microenvironment Remodeling by Intratumoral Oncolytic Vaccinia Virus Enhances the Efficacy of Immune-Checkpoint Blockade

“…Previous studies have reported that although the combination of an oncolytic virus and ICIs elicits an impressive immune response, the therapeutic efficacy can be affected by administration route and treatment schedule (22,41,48). In particular, when both the oncolytic virus and ICIs are systemically administered simultaneously, the combination could be antagonistic because of the ICI-induced antiviral immunity that can facilitate premature viral clearance, indicating the importance of an adequate time gap in between treatments for the oncolytic virus to induce a successful anticancer immunity (41,49). In the present study, local injection of JX consistently induced anticancer immunity without being significantly affected by administration sequences.…”

Immunogenic cell death in cancer therapy: Present and emerging inducers

“…WR (VV WR /TK ‐ RR ‐ ‐FCU1) is an engineered vaccinia virus. After injection of WR into MCA205 sarcoma cells in C57BL/6 mice, researchers found a trend of increasing calreticulin exposure, increased release of ATP and CXCL 10, which drove chemokine secretion that subsequently recruited T cells and presentation of tumour antigen to T cells by activated APCs . However, when OVs are combined with traditional ICD inducers, such as MIT or oxaliplatin, they potentiate antitumour effects and even break cancer immune tolerance.…”

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

“…97 We characterized a naturally-occurring preclinical model of cancer that exhibits intrinsic resistance against mitoxantrone-induced ICD in vivo secondary to a defect in CALR exposure, 199 and we documented that anthracyclines and oxaliplatin can trigger a necroptotic variant of ICD [211][212][213][214][215] in cancer cells expressing receptor interacting serine/threonine kinase 3 (RIP3K) and the pseudokinase mixed lineage kinase domain-like (MLKL). 215 Finally, we found that an engineered oncolytic vaccinia virus 216 can induce ICDdependent antitumor immunity, which can be further potentiated by the co-administration of ICD-inducing chemotherapy or immune checkpoint blockers (ICBs), 216 and that pharmacological inhibition of signal transducer and activator of transcription 3 (STAT3) 217 signaling boosts the therapeutic efficacy of anthracyclines upon increased type I interferon (IFN) secretion. 217 Pfirschke and co-authors (from Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA) found that autochthonous tumors lacking tumorinfiltrating lymphocytes (TILs) can be sensitized to immunological rejection via a Toll-like receptor 4 (TLR4)-dependent mechanism when suitable ICD inducers like oxaliplatin or cyclophosphamide are combined with ICBs targeting programmed cell death 1 (PDCD1; best known as PD-1) 218 and/or cytotoxic T-lymphocyte associated protein 4 (CTLA4).…”