Table 3.
Summary of oHSVs incorporating gene regulated or receptor retargeting mutations
| oHSV name | Parental HSV-1 | Gene(s) mutated | Description | Reference |
|---|---|---|---|---|
| G92A | KOS | UL23, RS1 |
UL23 gene replaced by LacZ driven by the unremoved UL23 promoter. Mouse albumin enhancer/promoter driving expression of RS1 in liver cancer. |
54 |
| d12.CALP | KOS | UL23, RS1 | Same as G92A except 4F2 heavy chain enhancer and calponin promoter driving expression of RS1 in soft tissue and bone cancer. | 55 |
| LCSOV | SC16 | UL22 | Apolipoprotein E enhancer/a1 antitrypsin promoter and four copies each of target sequences for miR-122a, miR-124a, and miR-let-7a driving expression of UL22 in liver cancer. | 56 |
| Myb34.5 | MGH-1 | RL1, UL39 | LacZ insertion in UL39 replaced with B-myb promoter driving expression of RL1. | 57 |
| rQNestin34.5 | MGH-1 | RL1, UL39 | LacZ insertion in UL39 replaced with Nestin enhancer, hsp68 promoter driving expression of RL1 in glioma. | 58 |
| AU27 | KOS | UL54 | Probasin promoter and rat fibroblast growth factor 5′UTR driving expression of UL54 in prostate cancer. | 63 |
| CMV-ICP4-143T/145T | 17 | RS1 | CMV promoter and five copies of target sequences for miR-143 or miR-145 driving expression of RS1 in prostate cancer. | 66 |
| AP27i145 | KOS | UL54 | CMV promoter and four copies of the target sequence for miR-145 driving expression of UL54 in non-small-cell lung cancer. | 67 |
| R5141 | F | UL27, UL44, US6 | Heparan sulfate binding in gB and gC abolished. IL13 inserted into gC and gD to allow binding to IL13Ra2 receptor overexpressed in glioblastoma and astrocytoma. gD no longer binds viral entry receptors HVEM and nectin. | 71 |
| R-LM249 | F | US6 | Sequence for trastuzumab antibody inserted in gD allows binding to HER-2 receptor overexpressed in breast and ovary cancer. gD no longer binds viral entry receptors HVEM and nectin. | 73 |
| HSV1716EGFR | 1716 | US6 | Sequence for single chain antibody for EGFR replaced N-terminus of gD. | 74 |
| KNE | KOS | UL27, US6 | Sequence for single chain antibody inserted in gD allows binding to overexpressed EGFR in glioblastoma. gD no longer binds viral entry receptors HVEM and nectin. Substitutions in gB lowered threshold for initiation of fusion. |
75 |
| R-VG809 | F | UL22, US6 | Sequence for trastuzumab antibody inserted in gH allows binding to HER-2 receptor overexpressed in breast and ovary cancer. gD no longer binds viral entry receptors HVEM and nectin. | 76 |
Abbreviations: CMV, cytomegalovirus; EGFR, epidermal growth factor receptor; g, glycoprotein; HER-2, human epidermal growth factor receptor 2; HSV-1, herpes simplex virus type 1; HVEM, herpesvirus entry mediator; ICP, infected cell protein; IL, interleukin; oHSV, oncolytic herpes simplex virus; RL, repeat long; RS, repeat short; UL, unique long; US, unique short.