Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy
Abstract
:1. Introduction
2. Attenuated oHSVs
2.1. Conditionally Replicating oHSVs with Single or Multiple Mutations
oHSV Name (Alternative Name) | Genetic Modification | Diagram in Figure 1, Line | Clinical Trial Identifier (Status) | Ref. |
---|---|---|---|---|
Conditionally replicating oHSVs with single or multiple mutations | ||||
dlsptk | deletion of UL23 (encodes TK) | a | – | [28] |
hrR3 | inactivation of UL39 (encodes ICP6, large subunit of RR) by lacZ insertion | b | – | [29] |
NV1020 (R7020) | deletion of one copy of γ134.5 (encodes ICP34.5 neurovirulence factor, anti-PKR) + HSV-2 US2-US8 genes + α4-tk | c | NCT00149396 (C) | [31] |
HF10 | duplications of UL53, UL54, UL55; deletion of UL56 | d | NCT02428036 (C) | [41] |
R3616 | deletion of two copies of γ134.5 (encodes ICP34.5 neurovirulence factor, anti-PKR) | e | – | [32] |
1716 | deletion of two copies of γ134.5 (encodes ICP34.5 neurovirulence factor, anti-PKR) | f | NCT00931931 (C) | [33] |
G207 | deletion of two copies of γ134.5 (encodes ICP34.5 neurovirulence factor, anti-PKR); inactivation of UL39 (encodes ICP6, large subunit of RR) by lacZ insertion | g | NCT00028158 (C) | [30] |
G47Δ | deletion of two copies of γ134.5 (encodes ICP34.5 neurovirulence factor, anti-PKR); deletion of US12 (encodes ICP47, immune evasion protein); increased expression of US11 (encodes anti-PKR factor) | h | UMIN000015995 (C) | [46] |
C134 | deletion of two copies of γ134.5 (encodes ICP34.5 neurovirulence factor, anti-PKR); insertion of HCMV IRS1 gene (inhibits antiviral state in the host cell) | i | NCT03657576 (A) | [47] |
Tumor-specific transcriptionally targeted oHSVs | ||||
rQNestin (rQNestin34.5v.2) | γ134.5 (encodes ICP34.5 neurovirulence factor, anti-PKR) under control of nestin promoter | j | NCT03152318 (R) | [48] |
NG34 | GADD34 (human counterpart of γ134.5) under control of nestin promoter | k | – | [49] |
2.2. Armed oHSVs
2.3. Talimogene Laherparepvec (T-VEC)
3. Tropism Retargeted, Unattenuated, oHSVs
4. oHSV Delivery
5. oHSV Combination Therapies and Immunotherapies
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
3-OS HS | 3-O-sulphated heparan sulphate |
BAC | bacterial artificial chromosome |
BIRC5 | baculoviral inhibitor of apoptosis repeat-containing 5 |
CEA | carcinoembryonic antigen |
CTL | cytotoxic T lymphocyte |
CTLA-4 | CTL antigen-4 |
CYP2B1 | cytochrome P450, family 2, subfamily b, polypeptide 1 |
EGFP | enhanced green fluorescent protein |
EGFR | epidermal growth factor receptor |
EGFRvIII | epidermal growth factor receptor variant III |
EMA | European Medicines Agency |
FDA | Food and Drug Administration (USA) |
GALV | gibbon ape leukemia virus |
GBM | glioblastoma multiforme |
GM-CSF | granulocyte macrophage colony-stimulating factor (GM-CSF) |
GMP | Good Manufacturing Practice |
GSCs | glioblastoma stem-like cells |
HCMV | human cytomegalovirus |
HER2 | human epidermal growth factor receptor 2 |
HS | heparan sulphate |
HveA | herpesvirus entry mediator A |
HveC | herpesvirus entry mediator C |
HVEM | herpesvirus entry mediator |
ICI | immune-checkpoint inhibitor |
ICP | infected cell protein |
IL | interleukin |
MAG | myelin-associated glycoprotein |
NMHC-II | non-muscle myosin heavy chain II |
N-ter | amino terminus |
OPTiM | OncoVEXGM-CSF Pivotal Trial in Melanoma |
OV | oncolytic virus |
PD-1 | programmed cell death 1 |
PD-L1 | programmed cell death 1 ligand 1 |
PILRα | paired immunoglobulin-like type 2 receptor-α |
PKR | protein kinase R |
PSMA | prostate-specific membrane antigen |
RR | ribonucleotide reductase |
scFv | single chain antibody variable fragment |
ScGCs | serum-cultured GBM cells |
TK | thymidine kinase |
UL | unique long |
uPA | urokinase-type plasminogen activator |
uPAR | urokinase-type plasminogen activator receptor |
US | unique short |
wt | wild type |
yCD | yeast cytosine deaminase |
Δ | deletion |
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oHSV Name | Expressed Transgene @ Viral Locus | Parental Virus | Diagram in Figure 2, Line | Clinical Trial Identifier (Status) | Ref. |
---|---|---|---|---|---|
R8306 | murine IL-4 @ γ134.5 loci | HSV-1(F), Δ 2 copies of γ134.5 | a | – | [69] |
M002 | murine IL-12 @ γ134.5 loci | HSV-1(F), Δ 2 copies of γ134.5 | b | – | [70] |
M032 | human IL-12 @ γ134.5 loci | HSV-1(F), Δ 2 copies of γ134.5 | c | NCT02062827 (R) | [71] |
NV1042 | murine IL-12 @ γ134.5 locus | NV1020 (Δ 1 copy of γ134.5) | d | – | [72] |
NV1034 | murine GM-CSF @ γ134.5 locus | NV1020 (Δ 1 copy of γ134.5) | e | – | [72] |
JS1/ICP34.5-/ICP47-/GM-CSF | murine GM-CSF @ γ134.5 loci | JS-1 1, Δ 2 copies of γ134.5, ΔUS12 | f | – | [73] |
OncoVEXGM-CSF, T-VEC, talimogene laherparepvec | human GM-CSF @ γ134.5 loci | JS-1 1, Δ 2 copies of γ134.5, ΔUS12 | g | NCT00769704 (C) | [74] |
Synco-1 | GALV fusogenic protein @ packaging signal | HSV-1, Δ 2 copies of γ134.5 | h | – | [62] |
rRp450 | rat CYP2B1 @ UL39 | HSV-1 (KOS) + inactivated UL39 | i | NCT01071941 (R) | [63] |
HSVyCD | yCD @ UL39 | HSV-1 (KOS) + inactivated UL39 | j | – | [64] |
OncoVEXCD | Fcy::Fur fusion @ γ134.5 locus | JS-1 1, Δ 2 copies of γ134.5, ΔUS12 | k | – | [65] |
Retargeting Ligand(s) @ Viral Glycoprotein | Target Heterologous Receptor | oHSV Name | Parental Strain | Ref. |
---|---|---|---|---|
@ gD | ||||
IL-13 @ gD aa 24 | IL-13Rα2 | R5111 | HSV-1(F) | [120] |
uPA @gD aa 24 | uPAR | R5181 | HSV-1(F) | [121] |
IL-13 @ gD Δ1-32 | IL-13Rα2 | R5141 | HSV-1(F)+gDV34S | [122] |
scFv to HER2 @ gD aa24 | HER2 | R-LM11 | HSV-1(F)BAC+lacZ | [123] |
scFv to HER2 @ gDΔ6-38 | HER2 | R-LM113 1 | HSV-1(F)BAC+EGFP | [124] |
scFv to HER2 @ gDΔ61-218 | HER2 | R-LM249 1 | HSV-1(F)BAC+EGFP | [125] |
scFv to CEA @ gDΔ2-24 | CEA | KNC 1 | HSV-1(KOS)+gDY38C+gB:NT allele | [126] |
scFv to EGFR @ gDΔ2-24 | EGFR, EGFRvIII | KNE 1 | HSV-1(KOS)+gDY38C+gB:NT allele | [126] |
scFv to EGFR @ gDΔ6-38 | EGFR | R-611 1 | HSV-1(F)BAC+EGFP | [127] |
scFv to PSMA @gDΔ6-38 | PSMA | R-593 1 | HSV-1(F)BAC+EGFP | [127] |
scFv to EGFRvIII @ gDΔ6-38 | EGFRvIII | R-613 1 | HSV-1(F)BAC+EGFP | [127] |
@ gD (double engineering) | ||||
scFv to HER2 and GCN4 peptide @ gD aa 24, or @ gDΔ35-39, or @ gDΔ214-223 | HER2 and GCN4R | R-87 1, R-89 1, R-97 1, R-99 1 | HSV-1(F)BAC+EGFP | [128] |
@ gH | ||||
scFv to HER2 @ gH aa 23 | HER2 | R-VG809 2 | HSV-1(F)BAC+mCherry+gDΔ6-38 | [129] |
GCN4 peptide @ gH aa 23 | HER2 and GCN4R | R-213 2 | R-LM113 | [130] |
@ gB | ||||
scFv to HER2 @ gB aa 43 | HER2 | R-909 2 | HSV-1(F)BAC+EGFP+gDΔ6-38 | [131] |
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Menotti, L.; Avitabile, E. Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy. Int. J. Mol. Sci. 2020, 21, 8310. https://doi.org/10.3390/ijms21218310
Menotti L, Avitabile E. Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy. International Journal of Molecular Sciences. 2020; 21(21):8310. https://doi.org/10.3390/ijms21218310
Chicago/Turabian StyleMenotti, Laura, and Elisa Avitabile. 2020. "Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy" International Journal of Molecular Sciences 21, no. 21: 8310. https://doi.org/10.3390/ijms21218310