Combination of novel oncolytic herpesvirus with paclitaxel as an efficient strategy for breast cancer therapy

Abstract

Background: New strategies are needed to improve the treatment of patients with breast cancer (BC). Oncolytic virotherapy is a promising new tool for cancer treatment but still has a limited overall durable antitumor response. A novel replicable recombinant oncolytic herpes simplex virus type 1 called VG161 has been developed and has demonstrated antitumor effects in several cancers. Here, we explored the efficacy and the antitumor immune response of VG161 cotreatment with paclitaxel (PTX) which as a novel oncolytic viral immunotherapy for BC. Methods: The antitumor effect of VG161 and PTX was confirmed in a BC xenograft mouse model. The immunostimulatory pathways were tested by RNA-seq and the remodeling of tumor microenvironment was detected by Flow cytometry analysis or Immunohistochemistry. Pulmonary lesions were analyzed by the EMT6-Luc BC model. Results:In this report, we demonstrate that VG161 can significantly represses BC growth and elicit a robust antitumor immune response in a mouse model. The effect is amplified when combined with PTX treatment. The antitumor effect is associated with the infiltration of lymphoid cells, including CD4 + T cells, CD8 + T cells, and NK

The combination therapy of oncolytic virotherapy

“…Theoretically, the combination of oncolytic viruses and PD-1/PD-L1 inhibitors can overcome these limitations by improving the tumor immune microenvironment. In preclinical studies, the novel oncolytic virus VG161, when used in combination with PD-1 monoclonal antibody, demonstrates significant synergistic effects in a mouse model of pancreatic cancer ( Deng et al, 2023 ; Shen et al, 2023 ). Single-cell sequencing and flow cytometry experiments have revealed that VG161 promotes the infiltration of CD8 + T cells and natural killer (NK) cells into the tumor, thereby altering the tumor’s immune microenvironment and providing a conducive setting for the subsequent use of PD-1 monoclonal antibody.…”