Anti-metastatic effects of DNA vaccine encoding single-chain trimer composed of MHC I and vascular endothelial growth factor receptor 2 peptide.
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-2Db [pcDNA3.1(+)-KDR2-β2m-H-2Db, 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.
Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang 310015, P.R. China.
Ruiling
R
Chen
Section Three of the Department of General Surgery, First Affliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832008, P.R. China.
Shengchao
S
Wang
Department of Microbiology and Immunology, Huzhou Teacher's College School of Medicine, Huzhou, Zhejiang 313000, P.R. China.
Yunliang
Y
Yao
Department of Pathogen Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
Yun
Y
Zhou
Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang 310015, P.R. China.
Chong
C
Zhang
Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang 310015, P.R. China.
Jie
J
Fang
Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang 310015, P.R. China.
Dayong
D
Zhang
Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang 310015, P.R. China.
Lihuang
L
Zhang
Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang 310015, P.R. China.
Jianping
J
Pan
D020533:Angiogenesis Inhibitors / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D064532:Histocompatibility Antigen H-2D / Q000235:genetics*; D006801:Humans; D007114:Immunization; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics
D020533:Angiogenesis Inhibitors; D064532:Histocompatibility Antigen H-2D; D019444:Vaccines, DNA; D001613:beta 2-Microglobulin; D040301:Vascular Endothelial Growth Factor Receptor-2