Intratumoral Delivery of a PD-1-Blocking scFv Encoded in Oncolytic HSV-1 Promotes Antitumor Immunity and Synergizes with TIGIT Blockade

Cancer Immunology Research
Chaolong LinNingshao Xia

Abstract

Oncolytic virotherapy can lead to systemic antitumor immunity, but the therapeutic potential of oncolytic viruses in humans is limited due to their insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). Here, we showed that locoregional oncolytic virotherapy upregulated the expression of PD-L1 in the TME, which was mediated by virus-induced type I and type II IFNs. To explore PD-1/PD-L1 signaling as a direct target in tumor tissue, we developed a novel immunotherapeutic herpes simplex virus (HSV), OVH-aMPD-1, that expressed a single-chain variable fragment (scFv) against PD-1 (aMPD-1 scFv). The virus was designed to locally deliver aMPD-1 scFv in the TME to achieve enhanced antitumor effects. This virus effectively modified the TME by releasing damage-associated molecular patterns, promoting antigen cross-presentation by dendritic cells, and enhancing the infiltration of activated T cells; these alterations resulted in antitumor T-cell activity that led to reduced tumor burdens in a liver cancer model. Compared with OVH, OVH-aMPD-1 promoted the infiltration of myeloid-derived suppressor cells (MDSC), resulting in significantly higher percentages of CD155+ granulocytic-MDSCs (G-MDSC) and monocytic-M...Continue Reading

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Citations

Nov 25, 2020·Expert Opinion on Drug Discovery·Shunchuan Zhang, Samuel D Rabkin
Mar 5, 2021·Oncolytic Virotherapy·Hong-My Nguyen, Dipongkor Saha
Apr 13, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Peter Kok-Ting WanLeonard W Seymour
Apr 24, 2021·World Journal of Gastrointestinal Oncology·Ming-Cheng GuanTian Yang
May 18, 2021·Frontiers in Immunology·Kari A ShaverAlicja J Copik

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