Replication and Spread of Oncolytic Herpes Simplex Virus in Solid Tumors

Abstract

Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for an oHSV for melanoma, but barriers to this promising therapy still exist that limit efficacy. The process of infection, replication and transmission of oHSV in solid tumors is key to obtaining a good lytic destruction of infected cancer cells to kill tumor cells and release tumor antigens that can prime anti-tumor efficacy. Intracellular tumor cell signaling and tumor stromal cells present multiple barriers that resist oHSV activity. Here, we provide a review focused on oncolytic HSV and the essential viral genes that allow for virus replication and spread in order to gain insight into how manipulation of these pathways can be exploited to potentiate oHSV infection and replication among tumor cells.

The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1

“…When designing an oHSV, many aspects must be taken into account, including the safety or efficacy resulting from the gene deletions, the possible transgene(s), the potential for combinatorial treatment, and additional delivery or targeting methods (reviewed in [23]). However, the aspect of choosing the parental virus is often neglected.…”

Imunoviroterapia oncolítica com Herpesvírus Simplex tipo I em tumores cerebrais malignos

“…O gene comummente eliminado γ34.5 codifica a proteína ICP34.5, o que permite ao vírus escapar à resposta de paragem da síntese proteica para que se possa espalhar sem problemas. Isto ocorre com o HSV-1 do tipo selvagem (WT), no entanto, no HSV-1 modificado, ambas as cópias deste gene são eliminadas (Hong et al, 2022).…”

The complex relationship between integrins and oncolytic herpes Simplex Virus 1 in high-grade glioma therapeutics

“…oHSV has been re-targeted and combined with other therapies for the treatment of HGG, 8 and the modulation of cell-intrinsic barriers has been explored to leverage this therapy. 76 Talimogene laherparepvec (T-Vec) is currently FDA approved for the treatment of metastatic melanoma and was shown to provide a 26% overall response rate in metastatic melanoma patients, with measurable increases in CD8 + T cells and decreases in regulatory T cells in biopsies of regressing lesions in a phase II clinical trial. 77 , 78 At the time of application, T-Vec showed a significant improvement in OS and suppression of tumor growth, a favorable response attributed to the generation of an antitumor immune response.…”