TABLE 2.
Selected preclinical studies of antiangiogenic reagents in combination with immunotherapies
| Antiangiogenic therapy | Immunotherapy | Tumormodel | Key results (arrows indicate increase/decrease) | References |
|---|---|---|---|---|
| Immune checkpoint blockade | ||||
| DC101 (Anti-VEGFR2) | 10F.9G2 (Anti-PD-L1) | Pancreatic cancer; breast cancer | Tumor burden;↓ animal survival;↑ lymphocyte infiltration↑ |
[144] |
| DC101 (Anti-VEGFR2) | RPM1–14 (Anti-PD-1) | Microsatellite-stable colorectal cancer | Animal survival;↑ antigen-specific T-cell response↑ |
[23] |
| Trebananib (Ang-1/Ang-2 peptibody); Aflibercept (VEGF-trap) | RPM1–14 (Anti-PD-1) | Glioblastoma | CD8+ T cells; ↑ vessel normalization↑ |
[145] |
| Axitinib | Anti-PD-1; Anti-TIM-3 | Colon cancer; Lewis lung carcinoma |
Mast cells;↓ TAMs;↓ T-cell response↑ |
[146] |
| B20-4.1.1 (Anti-VEGF) | RPM1–14 (Anti-PD-1) | Colon cancer | PD-1+CD8+ T cells; ↓ antitumor effect↑ |
[48] |
| VEGFR1-Fc | SIRPα-Fc | NSCLC | Resistance to antiangiogenic therapy;↓ macrophage phagocytosis;↑ animal survival↑ |
[147] |
| Tumor vaccines | ||||
| Sunitinib | OVA peptide-pulsed DC (VAC) | Melanoma | Antigen-specific T cells;↑ MDSCs;↓ Tregs↓ |
[159] |
| DC101 (Anti-VEGFR2) | HER-2 peptide vaccine | Breast cancer | Tumor growth;↓ lytic activity of CD8+ T cells ↑ |
[16] |
| DC101 (Anti-VEGFR2) | Whole cancer cell vaccine | Breast cancer | Animal survival↑ | [40] |
| Adoptive cell transfer | ||||
| NA | DC101-CAR T cells | Melanoma; colon cancer; fibrosarcoma | Tumor growth;↓ animal survival;↑ antigen-specific T cells;↑ MDSCs↓ |
[166] [167] [168] |
| DC101-CAR T cells | Tumor antigen-specific CAR T cells | Melanoma | Tumor regression;↑ infiltration and persistence of tumor-specific T cells↑ |
[169] |
| B20-4.1.1-PHAGE (Anti-VEGF); DC101 (Anti-VEGFR2) | Tumor antigen-specific CAR T cells | Melanoma | Antitumor effect;↑ infiltration of tumor-specific T cells↑ |
[170] |
| Bevacizumab (Anti-VEGF) | Cytokine-induced killer cells | NSCLC | Antitumor effect;↑ vessel normalization;↑ tumor hypoxia↓ |
[171] |
| STING agonist | ||||
| DC101 (Anti-VEGFR2) | cGAMP or ADU-S100; J43 (anti-PD-1); 9D9 (anti-CTLA-4) | Lewis lung carcinoma; Colon cancer; Breast cancer |
Tumor regression;↑ animal survival;↑ vessel normalization↑ |
[185] |
Abbreviations: DC, dendritic cell; MDSC, myeloid-derived suppressor cell; NSCLC, non-small cell lung cancer; TAM, tumor-associated macrophage; Treg, regulatory T cell. NA, not applicable.