Table 3.
Combination therapies in trans targeting tumor vasculature
| Target | Virus (species) | Antibody form | Effect ex vivo/in vivo | Delivery route (frequency) | Ref. |
| VEGF/ VEGFR | HF-10 (HSV) | Anti-VEGF IgG (bevacizumab) | Breast cancer/ s.c. in BLAB/c nude mice: ↓ MVD (IHC, CD31, 35 dpi); ↑ viral replication (IHC, HSV-1 antigen, 2, 35 dpi); ↑ hypoxia (IHC, HIF-α, 35 dpi) |
OV: i.t. (1) Ab: i.p. (4; twice a week from −1dpi to 13dpi) | 26 |
| VEGF/ VEGFR | hrR3 (HSV) | Anti-VEGF IgG (bevacizumab) | Gastric cancer/ s.c. in BALB/c nude mice: ↓ tumor mass; ↓ MVD (IHC, CD31, 12 dpi); ↑ viral replication (CSLM, LacZ, 12 dpi) |
OV: i.t. (4; 0, 3, 7, 10 dpi) Ab: IC (4; 0, 3, 7, 10 dpi) |
114 |
| VEGF/ VEGFR | rRp450 (HSV ICP-6 mutant) | Anti-VEGF IgG (bevacizumab) | Ewing sarcoma/ s.c. in nude mice: ↓ tumor mass; ↑ survival; ↓ MVD (IHC; CD31, 3 dpi); ↓ viral replication (plaque assay; 3 dpi); ↑ rescue of OV-depleted MHC class II TAM (FC; 3dpi) |
OV: i.t. (1) Ab: i.p. (1; 0 dpi) |
28 |
| VEGF/ VEGFR | CRAd-S-pk7 (Ad) | Anti-VEGF IgG (bevacizumab) | Glioma/ i.c. in nude mice: ↓ tumor mass; ↑ viral replication, distribution (IHC, hexon, 3 dpi) |
OV: i.c. (1) Ab: i.p. (2; −5 to –2 dpi) |
115 |
| VEGF/ VEGFR | dl992/947 (Ad) | Anti-VEGF IgG (bevacizumab) | Thyroid cancer/ s.c. in nude mice: ↓ tumor mass; ↓MVD (IHC, CD31, 2 dpi); ↑viral replication (IHC, Ad-GFP, 2 dpi) |
OV: i.t. (1) Ab: i.p. (2; −6 to –1 dpi) |
116 |
| VEGF/ VEGFR | GLV-1h68 (VV) | Anti-VEGF IgG (bevacizumab) | Lung, prostate cancer/ s.c. in nude mice: ↓ tumor mass; ↓ MVD (IHC, CD31, 21dpi) |
i.v. (1) i.p. (10; 2 times/week for 5 weeks from 13 dpi) |
5 |
| VEGF/ VEGFR | G47δ-mAngio (HSV armed with angiostatin) | Anti-VEGF IgG (bevacizumab) | Glioma/ s.t. in nude mice: ↓ tumor mass; ↑ survival; ↓ MVD (IHC; CD31; 3 dpi); ↓ viral replication, distribution (IHC, LacZ, 3 dpi); ↑ macrophage (IHC, F4/F80, 3dpi) |
OV: i.t. (1) Ab: i.v. (1; −2 dpi) |
27 |
Ab, antibody; Ad, adenovirus; CSLM, confocal laser scanning microscopy; dpi, days post-infection; EMH, extramedullary hematopoiesis; FC, flow cytometry; HER, HIF response elements; HIF, hypoxia inducible factor; HSV, herpes simplex virus-1; HUVEC, human umbilical vein endothelial cells; i.c., intracranial; IFN-γ, interferon-γ; IgG, immunoglobulin G; IHC, immunohistochemistry; i.p., intraperitoneal; i.t., intratumoral; i.v., intravenous; MHC, major histocompatibility complex; MVD, micro-vessel density; OV, oncolytic virus; Ref, reference; s.c., subcutaneous; s.t., stereotactic; TK, thymidine kinase; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; VV, vaccinia virus.