Combined therapy with flk1-based DNA vaccine and interleukin-12 results in enhanced antiangiogenic and antitumor effects

Immunotherapy against angiogenesis-associated targets: evidence and implications for the treatment of malignant glioma

“…Similar responses were observed in studies of DNA vaccines against PDGFR and VEGF [142,143]. Interestingly, later studies indicate that concurrent treatment with IL-12, a cytokine that augments T-cell proliferation, expanded the CTL response generated by the VEGFR2 DNA vaccine to include both endothelial and tumor cells in a mouse model of glioblastoma [144]. While each treatment alone displayed antivascular and antitumor effects, tumor regression was only observed in the combined treatment group.…”

Inhibition of angiogenesis by a Semliki Forest virus vector expressing VEGFR-2 reduces tumour growth and metastasis in mice

“…32,38 Indeed, recently it has been reported that immunization of mice with an attenuated Salmonella vector encoding Flk-1, combined with intramuscular injection of plasmid coding for IL-12, led to enhanced CTL responses against Flk-1. 35 However, in our study, this approach abrogated the therapeutic effect of rSFV-Flk-1 vaccination on tumour growth. It was also found that this combination strategy resulted in the elimination of the anti-Flk-1 antibody response seen following immunization with rSFV-Flk-1 VLPs alone.…”

“…Recently, several studies have demonstrated that active immunization of mice with Salmonella vectors or DC-based vaccines coding for or pulsed with Flk-1 protein/ peptides can inhibit tumour neovascularization and have an antimetastatic effect. 20,21,34,35 In each of these cases, a TH1-mediated CTL response against Flk-1 was detected. This approach is particularly attractive, as it specifically targets the genetically stable endothelial cell population and could conceivably be used against a variety of tumour types.…”

“…Although recently most preclinical studies have focused on the induction of T-cell responses to VEGFR-2 as a means to target tumour angiogenesis, 17,18,20,21,34,35 antibody-based therapies have proved to be clinically effective for the treatment of metastatic cancer. Bevacizumab (Avastin) is a monoclonal antibody specific for VEGF and has recently been approved by the FDA for treatment of patients with metastatic colorectal cancer.…”

Vascular Endothelial Growth Factor Receptor 2-Based DNA Immunization Delays Development of Herpetic Stromal Keratitis by Antiangiogenic Effects

“…It has been reported that immunization with recombinant Salmonella encoding Ags induces cytotoxic CD8 ϩ T cell response against the recombinant protein (30,36,39,40). It was suspected that the induction of CD8 ϩ T cell immunity against the VEGFR-2 protein was the mechanism by which the immunization with recombinant Salmonella encoding VEGFR-2 controlled HSV-induced angiogenesis and SK lesion severity.…”