Table 1.

Animal studies of combined treatment of vascular targeting and immunotherapy.

Agents	Target	Cancer Type	Immunomodulation and Response to Combining Immunotherapy
7C10 (anti-CD93 mAb)/2C6 (anti- IGFBP7)	CD93/IGFBP7	pancreatic cancer, melanoma	Intratumoral CD3+ T, NK, NKT cells ↑ Foxp3+ Treg, MDSC ↓ Tumor regression by combining with anti-PD-1/anti-CTLA-4 mAb Survival ↑ [104]
cGAMP (STING agonist)/DC101 (anti-VEGFR2 mAb)	STING, VEGFR2	LLC, colon cancer	CD8+ T, IFN-I ↑ Vessel normalization, anti-tumor immunity ↑ Tumor regression and survival ↑ [106]
B20-4.1.1 (anti-VEGF mAb)	VEGF	small cell lung cancer	PD-1+/TIM-3+ T cells ↓ by combining anti-VEGF with anti-PD-L1 Improved PFS and OS [113]
Sunitinib (VEGFR, TKI)	VEGFR1, R2, and R3	colorectal cancer	Exhaustion of CD8T ↓ Suppression of tumor growth by combining VEGF-A–VEGFR and PD-1 blockade [114]
DC101 (anti-VEGFR2 mAb)	VEGFR2	colorectal cancer	Restores anti-tumor activity of T cells by combining with anti-PD-1 mAb TAMs ↓ Tumor control ↑ [115]
DC101-CAR-T (scFv from anti-VEGFR2 mAb)	VEGFR2	melanoma, colon carcinoma, fibrosarcoma, renal cancer	Tumor infiltration of CAR-T ↑ Tumor growth ↓ Mice survival ↑ [109]
DC101-CAR-T (scFv from anti-VEGFR2 mAb +TCR against tumor antigens)	VEGFR2/tumor antigens	melanoma	Persistence of Ag-specific T cell infiltration ↑ Tumor-free survival ↑ Tumor growth ↓ [112]
CAR-T (anti-PSMA scFv)	Endothelial PSMA	ovarian cancer	Tumor vascular density ↓ Tumor regression ↑ [116]

↑ indicates increase in cell numbers, frequency or activity; ↓ denotes decrease in cell numbers or populations; IGFBP7: insulin-like growth factor binding protein 7; NK: natural killer; MDSC: myeloid-derived suppressor cells; STING: Stimulator of interferon genes; LLC: Lewis lung carcinoma; IFN-I: type I interferon; PFS: progression-free survival; OS: overall survival; scFv: single-chain variable fragment; Ag: antigen; PSMA: prostate-specific membrane antigen (PSMA); TKI: tyrosine kinase inhibitor; TAMs: tumor-associated macrophages.