Anti-metastatic effects of DNA vaccine encoding single-chain trimer composed of MHC I and vascular endothelial growth factor receptor 2 peptide

Abstract

Abstract. Vascular endothelial growth factor receptor 2 (VEGFR2)-mediated signaling is the key rate-limiting step in angiogenesis. VEGFR2 serves as the most important target of anti-angiogenic therapy for cancers. Single-chain trimer (SCT) comprising antigen peptide, β2-microglobulin (β2m), and major histocompatibility complex (MHC) class I heavy chain was a particularly powerful strategy involved in the increase of the potency of DNA vaccine against tumors and infections. In the present study, we constructed an SCT-encoding VEGFR2 antigen peptide [aa400-408, also known as kinase insert domain-containing receptor (KDR2)], β2m, and mouse MHC class I heavy chain H-2D b [pcDNA3.1(+)-KDR2-β2m-H-2D b , or SCT-KDR2]. The constructed SCT-KDR2 DNA was efficiently expressed in the human A293 embryonic kidney cell line. Intradermal immunization of C57BL/6 mice with SCT-KDR2 DNA was able to successfully break self-immunological tolerance and induce robust cytotoxic T-lymphocyte (CTL) response to VEGFR2, leading to marked suppression of tumor cell-induced angiogenesis and metastasis in murine models of B16 melanoma and 3LL Lewis lung carcinoma. Taken together, the results showed that VEGFR2-targeted SCT vaccination is an effective modality that can be utilized in anti-angiogenic active immunotherapy for various types of cancer.

Cancer DNA vaccines: current preclinical and clinical developments and future perspectives

“…Many recent preclinical studies have investigated the use of polyepitope DNA vaccines to reach a broad immune response. As a result, an increased IFNg production, a higher Th and CTL response [86, 87], and a general decrease in the tumor growth rate and metastasis formation were observed in different types of cancer models [88, 89]. Some preclinical studies focus on the HPV model, using DNA vaccines encoding E6 and E7 molecules [90], or E7 with a helper epitope [88].…”

Synergistic antitumor effect of a human papillomavirus DNA vaccine harboring E6E7 fusion gene and vascular endothelial growth factor receptor 2 gene

“…VEGF and its receptor VEGFR2 have become popular subjects for study because of their role in angiogenesis. A number of studies on antitumor therapy with VEGFR2 as the target have demonstrated significant effects, including inhibition of tumor angiogenesis, tumor growth, and metastasis .…”

Anti-angiogenic agents for the treatment of solid tumors: Potential pathways, therapy and current strategies – A review

“…Some anti-VEGF vaccines (CIGB-247: VEGF variant/bacterial adjuvant vaccine) showed reasonable tolerability in phase-I clinical trials with minimal hematopoietic or wound-healing impairments [151] . In addition, DNA and peptide based vaccines against VEGFR-2 showed potent humoral- and cellular-based anti-vascular immunity with subsequent anti-angiogenesis, anti-tumor and anti-metastatic responses [152] , [153] . These vaccines showed negligible adverse effects against wound healing and embryogenesis [153] .…”