Table 2. Selection of armed OVs.
For cancer, preclinical studies indicate cell line used, prefixed with h if human cell line.
| Therapeutic Transgene | Virus Name |
Modifications | Immunologic Effects (preclinical) | Cancer | Combinations | Clinical trial Reference |
|---|---|---|---|---|---|---|
| Cytokine | ||||||
| GM-CSF | HSV Talimogene laherparepvec (T-Vec) |
GM-CSF→γ34.5Δ / ICP47Δ | Produce granulocytes and monocytes | Melanoma Melanoma Breast Breast Breast Sarcoma Sarcoma Rectal |
Ipi Pembrolizumab Nivolumab Nivolumab +Ipi Paclitaxel Trabectedin Radiation Chemo +Radiation |
NCT01740297 NCT02263508 NCT04185311 NCT04185311 NCT02779855 NCT03886311 NCT03300544 NCT02923778 |
| HSV RP1 |
GM-CSF-GALV-GP-R→γ34.5Δ / ICP47Δ | Cutaneous SCC Cutaneous SCC Melanoma |
Cemiplimab Nivolumab |
NCT04349436 NCT04050436 NCT03767348 |
||
| VV JX-594 (Pexa-Vec) |
Wyeth VV LacZ-hGM-CSF→TKΔ | Differentiate monocytes into DCs | Solid tumors Solid tumors HCC Colorectal Breast, sarcoma |
Ipi Sorafenib Irinotecan CPA |
NCT01636284 NCT02977156 NCT02562755 NCT01394939 NCT02630368 |
|
| Ad CG0070 (Ad5/3-D24-GMCSF) |
Ad5 E2F-1pro-E1A / GM-CSF→E3-19kΔ | Recruit NK cells, induce tumor-specific CTLs | Bladder Bladder |
Pembrolizumab |
NCT02365818 NCT04387461 |
|
| Ad ONCOS-102 |
Ad5/3 E1AΔ24 / GM-CSF→E3-19kΔ | Peritoneal Melanoma Mesothelioma |
Durvalumab Pembrolizumab CPA + carboplatin |
NCT02963831 NCT03003676 NCT02879669 |
||
| NDV MEDI5395 |
F mutation / GM-CSF→P-M | Myeloid cell infection, proinflammatory cytokines | Solid tumors | Durvalumab | NCT03889275 | |
| IL-12 | HSV G47Δ-IL12 |
G47Δ / LacZ -mIL-12→ICP6− | Increased M1 macrophages, Teff/Treg | Glioblastoma | anti-PD-1, anti-CTLA-4 | [142] |
| HSV M032 |
hIL-12→γ34.5Δ | Activate T & NK cells | Glioma | NCT02062827 | ||
| HSV NV1042 |
HSV1-HSV2 recombinant / UL56Δ / IRΔ | Prostate, breast | [96] | |||
| Ad Ad-TD-nsIL-12 |
Ad5 E1A CR2Δ / E1B-19kΔ / non-secreting IL-12→E3-19kΔ | NK and CTL activities | Pancreatic (Syrian hamster) | [98] | ||
| VV vvvDD-IL-12FG |
Tethered IL-12, YFP→TKΔ / VGFΔ | Increased TILs, decreased Treg, MDSCs | Colon MC38 | anti-PD-1 | [99] | |
| VSV rVSV-IL12 |
p35-IRES-p40 | murine SSC VII | [94] | |||
| IL-2 | VV vvDD-IL2-RG |
GPI-IL-2, YFP→TKΔ / VGFΔ | Increased CD8+/Treg ratio | MC38, | anti-ICI | [100] |
| NDV rLaSota/IL12 |
Increased TILs and CTL | B16 melanoma, H22 HCC | [101] | |||
| IL-15 | VV vvDD-IL5Rα |
IL-15Rα-IL15, YFP→TKΔ / VGFΔ | Increased CTL and memory | B16, ID8 ovarian | anti-PD-1 | [178] |
| MYXV vMyx-IL5Rα-tdTr- |
IL-15Rα-IL15, tdTomatoRed | Increased T and NK cell | B16 | [179] | ||
| Influenza A (IAV) aT116-IL-15 |
IL-15-2A FMDV-NS1Δ | Increased NK, memory CD8+ T cells, CTL | B16 | [30] | ||
| VSV opt.hIL-15 |
MΔM51 / Ig leader-hIL-15 | Increased NK and T cell responses | CT26 lung mets | [30] | ||
| IFNα / β | VSV VSV-hINFβ |
Liver | NCT01628640 | |||
| VSV VSV-hINFβ-NIS (Voyager-V1) |
Endometrial Myeloma, lymphoma NSCLC, head & neck Solid tumors |
Ruxolitinib Pembrolizumab Cemiplimab |
NCT03120624 NCT03017820 NCT03647163 NCT04291105 |
|||
| Ad KD3-IFNα |
Ad5 E1A-2 small Δ / E3Δ / ADPhi / hIFNα | h Hep3B | [104] | |||
| RGD-Cox2-ΔE3-ADP-ham-IFN | Ad5 Cox2pro-E1A / E3Δ / ADPhi / hamster IFN /RGD fiber | Syrian hamster pancreatic | [180] | |||
| VV JX-795 |
B18RΔ / mIFNβ→TKΔ | CMT-93 | [105] | |||
| TRAIL | Ad H5CmTERT-AdTRAIL |
HRE-Myc site-TERTpro-E1A-RbΔ / E1B-19kΔ / stTRAIL→E3 | Increased apoptosis | h U87 | [181] | |
| HSV G47Δ-TRAIL |
γ34.5Δ / LacZ, sTRAIL→ICP6− / ICP47Δ | Increased apoptosis | h GSCs | [182] | ||
| NDV NDV/Anh-TRAIL |
sTRAIL | Increased apoptosis, T cells | H22 hepatoma | [183] | ||
| Chemokine | ||||||
| CCL5 (RANTES) | VV vvCCL5 |
mCCL5, DsRed→TKΔ / VGFΔ | Increased TIL and DC | MC-38 | [108] | |
| Ad Ad-RANTES-E1A |
CCL5-IRES-E1A / E1BΔ | Increased CTL, infiltrating/activate DC | JC mammary, E.G-7 lymphoma | [107] | ||
| CCL19 | VV vvCCL19 |
mCCL19, DsRed→TKΔ / VGFΔ | Increased CD4+ TILs and DCs | MC-38 | [109] | |
| CXCL9 | VSV VSV-CXCL9 |
M51R / hCXCL9 mCXCL9 |
No significant effects | h FaDu 5TGM1 |
[112] | |
| Immune Checkpoint Inhibitors (ICI) | ||||||
| CTLA-4 | Ad Ad5/3-Δ24aCTLA4 |
Ad5/3 E1AΔ24 / anti-hCTLA-4 mAb→E3Δ | Increased hPBMC IL2/IFNγ | [30] | ||
| MV MV-aCTLA-4 |
anti-mCTLA-4 scFv / EGFP | B16-CD20 | [117] | |||
| PD-1 | HSV oHSV2-aPD1 |
anti-hPD-1 mAb→ γ34.5Δ / ICP47Δ | Increased effector splenocytes | B16R | [118] | |
| HSV OVH-aMPD-1 |
anti-mPD-1 scFv→γ34.5Δ / ICP0Δ /hTERTpro-ICP27 | Increased effector T cells, MDSCs | Hepa1-6 | anti-TIGIT | [116] | |
| VV WR-mAb1 WR-scFv |
WR VV RR (I4L)Δ / anti-hamster PD-1→TKΔ | MCA 205 | [115] | |||
| MYXV vPD1 |
sPD1-extracellular, GFP | Enhanced tumor-specific CD8+ activation | B16 | [30] | ||
| PD-L1 | VSV VSVM51R-PD-L1 |
M51R / anti-hPD-L1 scFv | Increased activated CD8+ splenocytes | LLC-hPD-L1 | [114] | |
| Co-stimulatory agonists | ||||||
| CD40L | Ad AdCD40L (CGTG-401) |
Ad5/3 hTERTpro-E1A / CD40L→E3Δ | Melanoma | CPA | NCT01455259 | |
| CD40 | Ad NG-350A |
EnAd anti-CD40 agonist | Epithelial | NCT03852511 | ||
| OX40L | Ad DNX-2440 (Delta-24-RGDOX) |
Ad5 E1AΔ24 / OX40L→E3Δ / RGD-fiber | Glioblastoma | NCT03714334 | ||
| 4-1BBL | VV rV-4-1BBL |
LacZ, 4-1BBL→TK− | Increased CD8+ TILs | B16 | Lymphodepletion | [30] |
| ICOSL | NDV NDV-ICOSL |
NDV LaSota mICOSL | Increased TILs | B16 | anti-CTLA-4 | [125] |
| GITRL | Ad Delta-24-GREAT |
Ad5 E1AΔ24 / mGITRL→E3Δ / RGD-fiber | Increased CD8+ TILs | GL261 | [122] | |
|
T-cell engager (BiTE) |
||||||
| VV EphA2-TEA-VV |
anti-EphA2 scFV-anti-CD3 scFv, DsRed→TKΔ / VGFΔ | Bystander killing, T cell activation | h A549 + PBMCs | [129] | ||
| Ad oAd-BiTE (ICO15K-cBiTE) |
Ad5 E2F pro-E1AΔ24 / anti-hEGFR scFv-anti-CD3 scFv / RGD-fiber | Enhances CAR-T | h Panc-1, HCT116 | CAR-T cells | [134] | |
| Ad EnAd-SA-FAP |
EnAd anti-hFAP scFv-anti-CD3 scFv-RFP→E3Δ | Increased T cell activation, M1-macrophages, killed FAP+ | h malignant ascites | [132] | ||
| MV MV-mCD3xCEA MV-mCD3xCD20 |
anti-mCD3 scFv-anti-CEA (or CD20) scFv | Increased TIL, CD8+/Treg ratio | MC38-CEA, B16-CD20-CD46 | [130] | ||
| Tumor-associated antigens (TAAs) | ||||||
| Prostatic acid phosphatase (PAP) | HSV bPΔ6-hPAP |
HSV hPAP, LacZ→ICP6− | hPAP not mPAP more efficacious. | TRAMP-C2 | [138] | |
| MAGE-A3 | Maraba virus MG1-MA3 |
Maraba Gmut / Mmut / hMAGE-A3 | Ad-MAGEA3 prime - MG1 boost | MAGE-A3+ solid tumors Melanoma, SCC |
Ad-MAGEA3 Pembrolizumab |
NCT02285816 NCT03773744 |
| HPV E6, E7 | Maraba virus MG1-E6E7 |
Maraba Gmut / Mmut / HPV17, 18 E6–E7 | Ad-E6E7 prime - MG1 boost | HPV+ cancer | Ad-E6E7, Atezolizumab | NCT03618953 |
| Combinations | ||||||
| Ad LOAd703 |
Ad5/35 E2Fpro-E1AΔ24 / E3AΔ / trimerized membrane-bound hCD40L-T2A-h4-1BBL | Solid tumors Melanoma Pancreatic |
Atezolizumab Gem, Pac, Atezolizumab |
NCT03225989 NCT04123470 NCT02705196 |
||
| Ad TILT-123 |
Ad5/3 E2Fpro-E1AΔ24 / TNFα-IRES-IL2→E3Δ | NCT04217473 | ||||
| VV TBio-6517 |
IL-12, anti-CTLA-4, Flt3L | Solid tumors | Pembrolizumab | NCT04301011 | ||
| HSV ONCR-177 |
anti-PD-1-IL12, anti-CTLA-4-Flt3L-CCL4 / miR-T-UL8 / gBmut / UL37mut / miR-T-ICP27 / JointΔ / ICP47Δ / miR-T-ICP4 / miR-T-γ | Solid tumors | Pembrolizumab | NCT04348916 | ||
| Ad NG641 |
EnAd / CXCL9, CXCL10, IFNα, FAP-BiTE | Epithelial | NCT04053283 |
Abbreviations: Ad, adenovirus; Chemo, chemotherapy; CPA, cyclophosphamide; Δ, deletion; GSCs, glioblastoma stem-like cells; h, human; HCC, hepatocellular carcinoma; HGG, high grade glioma; HSV, herpes simplex virus; Ipi, ipilimumab; MV, measles virus; MYXV, Myxoma virus; NDV, Newcastle disease virus; NSCLC, non-small cell lung cancer; pro, promoter; SCC, squamous cell carcinoma; TMZ, temozolomide; VSV, vesicular stomatitis virus; VV, vaccinia virus