Table 5.
Application of HSV-1 as a therapeutic vector.
| Name | Diseases | Developmental Phase | characteristics | therapeutic mechanism | Refs |
|---|---|---|---|---|---|
| T-VEC (OncoVEXGM-CSF) |
human melanoma | Approved drugs | Genetically modified herpesviruses target cancer cells for replication, enhance immune response, promote antigen presentation, and induce systemic antitumor immune response. | Infected cancer cells replicate and cause lysis, release antigen-promoting immunity, GM-CSF helps recruitment, and T cells activate to kill tumours. | [205,206] |
| VC2 | mouse melanoma | Mouse model | VC2 Is an attenuated HSV-1 virus that removes gK (31-68 aa) and UL 20 (4-22 aa), retaining infectious capacity while reducing toxicity and improving safety, may be targeted and immunogenic, and suitable for specific studies or treatment | VC2 Infected cells have unique strategies and may enter through non-canonical receptors, using the remaining viral proteins and host metabolic replication, avoiding strong immune responses. Finally releasing the virus by lysis or apoptosis, infecting neighbouring cells, or triggering an immune response, the specific mechanism needs further investigation | [207] |
| OV-mOX40L | Pancreatic ductal adenocarcinoma (PDAC) | Mouse model | Combining oncolysis with immune enhancement, activating anti-tumour immunity, and regulating the immune microenvironment. | Virus lysis of tumour release antigen, T cell activation increases immunity, and microenvironment transformation to promote cancer | [208] |
| KB105 | Autosomal recessive congenital ichthyosis (ARCI) | Preclinical | KB105 is an HSV-1 based gene therapy that targets the TGM 1-deficient ARCI. The TGM 1 gene was delivered to the skin cells using the STAR-D technology to restore the protein function. As a non-integrated viral vector, with high loading and low immunogenicity, suitable for repeat delivery. | 1.Gene delivery: effective TGM 1 gene delivery to skin cells. 2.Gene expression: intracellular expression of TGM 1 protein. 3. Functional recovery: improve the skin barrier and reduce the symptoms of ichthyosis. 4.Immune regulation: low immunogenicity, reduces immune response, and promotes gene transmission and expression. |
[209] |
| G47Δ-mIL12 | triple-negative breast cancer (TNBC) | Mouse model | G47 Δ -mIL 12 is a genetically modified oncolytic virus based on triple mutant HSV-1, which carries the murine-derived IL-12 gene designed to enhance the specific killing of the tumour and activate the immune system. | 1. Oncolysis: infection and lysis of tumour cells. 2. Immune activation: express IL-12, activate T cells, NK cells, etc. 3. Microenvironment regulation: reduce immune suppression and increase anti-tumour immunity. 4. Synergism: used in combination with immune checkpoint inhibitors to improve the efficacy. |
[210] |
| B-VEC | Dystrophic epidermolysis bullosa (DEB) | Approved drugs | B-VEC is a non-invasive gene therapy for DEB. Gel dosage form, directly applied to the DEB wound, carrying the COL7A1 gene fragment by the HSV-1 vector | The COL7A1 gene fragment was introduced into skin cells to express COL 7 protein, restore the basement membrane band structure and function, and enhance skin junctions. Promote wound healing, reduce blisters and tears, and improve skin condition. | [211] |
| HSV-1dko-B7H3nb/CD3 | Glioblastoma (GBM) or colorectal adenocarcinoma (COAD) | mouse model | HSV-1dko-B7H3nb/CD3 is a genetically modified herpes simplex virus (HSV-1) vector with the properties of a dual gene knockout (dko) and the expression of a chimeric antigen receptor (CAR). It aims to specifically target and kill tumour cells by redirecting T cells. | CAR recognizes tumour B7H3, activates T cells, and releases toxins to kill the tumour and initiate antitumor immunity | [212] |