Beyond cancer cells: Targeting the tumor microenvironment with gene therapy and armed oncolytic virus

Abstract

Cancer gene therapies are usually designed either to express wild-type copies of tumor suppressor genes or to exploit tumor-associated phenotypic changes to endow selective cytotoxicity. However, these approaches become less relevant to cancers that contain many independent mutations, and the situation is made more complex by our increased understanding of clonal evolution of tumors, meaning that different metastases and even regions of the same tumor mass have distinct mutational and phenotypic profiles. In contrast, the relatively genetically stable tumor microenvironment (TME) therefore provides an appealing therapeutic target, particularly since it plays an essential role in promoting cancer growth, immune tolerance, and acquired resistance to many therapies. Recently, a variety of different TME-targeted gene therapy and armed oncolytic strategies have been explored, with particular success observed in strategies targeting the cancer stroma, reducing tumor vasculature, and repolarizing the immunosuppressive microenvironment. Herein, we review the progress of these TME-targeting approaches and try to highlight those showing the greatest promise.

BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

“…As TILs in tumor microenvironment (TME) is increasingly regarded as an effective tumor immunotherapy target, revealing its mechanism of action is the premise of individualized precision therapy at present ( Wan et al, 2021 ). Our data suggested that high expression of BTBD10 significantly affected immune response-related pathways, which could reveal the mechanism by which tumor cells evade immune response ( Sturm et al, 2019 ).…”

The role of NK cells in oncolytic viral therapy: a focus on hepatocellular carcinoma

“…The chief goals of OV therapy are replication-dependent oncolysis and activation of the immune system, although the TME can now also be considered a relevant therapeutic target [ 21 ] . Both the innate and adaptive arms of the immune response are modulated by OV therapy.…”

“…T-VEC is a recombinant herpes simplex virus type 1 (HSV-1) and encodes two copies of granulocyte-macrophage colony-stimulating factor using CMV-promoters. T-VEC can be used as a standalone treatment or combined with the PD-1 inhibitor pembrolizumab or the CTLA-4 inhibitor ipilimumab [19,20] .…”

Dacarbazine-Loaded Targeted Polymeric Nanoparticles for Enhancing Malignant Melanoma Therapy

“…It is considered to be the most promising method in cancer treatment. In recent years, new tumor-targeted strategies have emerged, such as tumor-targeted drug therapy ( Jin et al, 2021 ; Kerns et al, 2021 ; Li et al, 2021 ; Li et al, 2021 ), immunotherapy ( Chen et al, 2021 ; Lu et al, 2021 ; Pei et al, 2021 ), gene therapy ( Chada et al, 2015 ; Wang et al, 2021 ; Wang et al, 2021 ), virus therapy ( Kemler et al, 2021 ; Wan et al, 2021 ; Zhang et al, 2021 ), and cell-based targeted therapy ( Collet et al, 2016 ). Among them, tumor active targeted drug therapy based on nanoparticles (NPs) drug delivery systems achieved the most success.…”