. Author manuscript; available in PMC: 2015 Nov 10.

Published in final edited form as: Cancer Cell. 2014 Nov 10;26(5):605–622. doi: 10.1016/j.ccell.2014.10.006

Table 3. Combination of immunotherapies with antiangiogenic agents.

Antiangiogenic	Immunotherapy	Tumor models	Results
Preclinical studies
Anti-VEGFR2 mAb	Whole tumor cell vaccine (secreting GM-CSF)	Breast carcinoma (Neu-expressing)	↑ trafficking of CD8⁺ T cells ↑ regression of tumor in FVB mice (Manning et al., 2007)
Anti-VEGFR2 mAb	Whole tumor cell vaccine (Mitomycin treated)	Breast carcinoma	↑ recruitment of CD4⁺ and CD8⁺ T cells ↓ MDSCs and Tregs ↑ survival (Huang et al., 2012)
Adenoviral delivery of sVEGFR1/R2	Whole tumor cell vaccine (secreting GM-CSF)	Colon carcinoma Melanoma	↑ infiltration of CD4⁺ and CD8⁺ T cells. ↓ MDSCs and Tregs. ↑ survival (Li et al., 2006)
VEGF peptide mimic	HER-2 B cell epitope vaccine	Breast carcinoma	↑ High affinity HER-2 native antibodies. ↑anti-tumor and antiangiogenic effects. ↓ tumor growth (Foy et al., 2012)
SU 6668	Whole tumor cell vaccine (irradiated) and recombinant B7.2-IgG fusion protein	Breast carcinoma	↑ recruitment of CD8⁺ T cells (Huang et al., 2002)
Sunitinib	Pox-virus based vaccine expressing carcinoembryonic antigen (CEA) and costimulatory molecules	Colon carcinoma	↑ intratumoral T cells ↓ MDSCs and Tregs ↓ tumor volume and ↑ survival (Farsaci et al., 2012)
Sorafenib	Anti-PD-1 antibody with a CXCR4 inhibitor (AMD3100)	Hepatocellular carcinoma	↑ intratumoral T cells ↓ MDSCs and Tregs ↓ primary and metastatic tumor volume and ↑ apoptosis ^h
Anti-mouse VEGF mAb	Peptide-pulsed DCs	Sarcoma	↑ DC number and function. ↑ tumor growth delay (Gabrilovich et al., 1999)
Anti-mouse VEGF mAb	Anti-gp100 pmel-1 T cells, gp100 vaccine, IL-2 after lymphodepletion	Melanoma	↑ immune cell infiltration ↑ tumor growth delay ↑ survival (Shrimali et al., 2010)
Anti-mouse VEGF mAb	VEGFR-1 CAR-Modified T cells	Lung carcinoma	↓ endothelial tube formation in vitro ↑ tumor growth delay and ↓ metastasis (Wang et al., 2013)
Anti-VEGFR2	Anti-PD-1 antibody	Colon carcinoma	↑ inhibition of tumor neovascularization. ↑ T cell infiltration. ↑ expression of cytokines (Yasuda et al., 2013)
Clinical Studies
N/A	Peptide vaccine (VEGFR1, VEGFR2, URLC10, TTK or CDCA1)	NSCLC	↑ T cell response ↑ Stable disease for 2 months (Suzuki et al., 2013)
N/A	Antiangiogenic peptide vaccine	Different solid tumors	↑ activation of T cells. Anti-tumor activity being evaluated (Hayashi et al., 2013)
Sunitinib	Adoptive T cell transfer	RCC	↓ number and function of MDSCs and Tregs (Ko et al., 2009)
Bevacizumab	IFN-aplha2A	Metastatic RCC	↑ progression free survival (Escudier et al., 2010)
Bevacizumab	Ipilimumab	Advanced melanoma	↑ T cell infiltration (Hodi et al., 2014)
Bevacizumab	Nivolumab	NSCLC	(clinicaltrials.gov identifier: NCT01454102)
Bevacizumab	Nivolumab	GBM	(clinicaltrials.gov identifier: NCT02017717)

Reiberger, T., Ramjiawan, R. R., Chen, Y., Ng, R., Hato, T., Unan, E. C., Reddy, T. P., Huang, Y., Ochiai, H., Huang, P., Zhu, A. X., Jain, R. K., Duda, D. G. (2014). CXCR4 inhibition in combination with anti-PD1 immunotherapy results in an effective immune response during treatment with sorafenib in hepatocellular carcinoma. Hepatology 60(S1): 644A (abstract 920).