The Continued Promise and Many Disappointments of Oncolytic Virotherapy in Gastrointestinal Malignancies

Abstract

Oncolytic virotherapy represents a novel therapeutic strategy in the treatment of gastrointestinal malignancies. Oncolytic viruses, including genetically engineered and naturally occurring viruses, can selectively replicate in and induce tumor cell apoptosis without harming normal tissues, thus offering a promising tool in the armamentarium for cancer therapy. While this approach has garnered much interest over the past several decades, there has not been significant headway across various tumor types. The recent approval of talimogene laherparepvec, a second-generation oncolytic herpes simplex virus type-1, for the treatment of metastatic melanoma, confirms the therapeutic potential of oncolytic viral therapy. Herein, we will highlight and review the role of oncolytic viral therapy in gastrointestinal malignancies while discussing its limitations and potential alternative mechanisms to improve its treatment efficacy.

Editorial of the Special Issue: Oncolytic Viruses as a Novel Form of Immunotherapy for Cancer

“…Chaurasiya and Warner also summarize recent studies on combination therapies with immune checkpoint inhibitors or with CAR T cells. In another review, Aha and Bekaii-Saab discuss preclinical and clinical studies with OVs in gastrointestinal malignancies [ 20 ]. They discuss preclinical studies using oncolytic AdV, HSV, reovirus, VSV, and VV.…”

Oncolytic Viruses in Combination Therapeutic Approaches with Epigenetic Modulators: Past, Present, and Future Perspectives

“…T-Vec is a genetically modified HSV-1 with a deletion in γ-34.5 and α-47 genes and addition of two copies of the gene for the Colony Stimulating Factor of human Granulocyte-Macrophages (GM-CSF) [ 146 ]. Many ongoing clinical trials evaluate the efficacy of T-VEC alone or in combination with various other therapies [ 147 , 148 , 149 , 150 , 151 ], and its safety profile has been investigated in patients with various metastatic cancers, including breast, gastrointestinal, and melanoma [ 148 , 152 , 153 ]. In all, intralesional administration of T-Vec was well tolerated, without inducing strong symptoms and stimulating strong anti-cancer effects [ 154 ].…”

Expanding the Spectrum of Pancreatic Cancers Responsive to Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Challenges and Solutions

“…In this review, we will discuss current advances with OV therapy for PDAC, with a special focus on VSV, the major interest of our laboratory. While other OV will be discussed in the current review, we would like to refer to other reviews which give a more general overview of OV therapy for pancreatic cancer [ 115 , 116 , 117 , 118 ].…”