title: Synergistic antitumor efficacy of combined DNA vaccines targeting tumor cells and angiogenesis.
abstract: To further enhance the antitumor efficacy of DNA vaccine, we proposed a synergistic strategy that targeted tumor cells and angiogenesis simultaneously. In this study, a Semliki Forest Virus (SFV) replicon DNA vaccine expressing 1-4 domains of murine VEGFR2 and IL12 was constructed, and was named pSVK-VEGFR2-GFc-IL12 (CAVE). The expression of VEGFR2 antigen and IL12 adjuvant molecule in 293T cells in vitro were verified by western blot and enzyme-linked immune sorbent assay (ELISA). Then CAVE was co-immunized with CAVA, a SFV replicon DNA vaccine targeting survivin and β-hCG antigens constructed previously. The antitumor efficacy of our combined replicon vaccines was evaluated in mice model and the possible mechanism was further investigated. The combined vaccines could elicit efficient humoral and cellular immune responses against survivin, β-hCG and VEGFR2 simultaneously. Compared with CAVE or CAVA vaccine alone, the combined vaccines inhibited the tumor growth and improved the survival rate in B16 melanoma mice model more effectively. Furthermore, the intratumoral microvessel density was lowest in combined vaccines group than CAVE or CAVA alone group. Therefore, this synergistic strategy of DNA vaccines for tumor treatment results in an increased antitumor efficacy, and may be more suitable for translation to future research and clinic.
authors.affiliation: Department of Urology, Chinese PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China; Beijing Institute of Basic Medical Sciences, 27 Tai Ping Road, Beijing 100850, China.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Yin
authors.affiliation: Beijing Institute of Basic Medical Sciences, 27 Tai Ping Road, Beijing 100850, China; Department of Urology, No. 261 Hospital of PLA, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Beijing Institute of Basic Medical Sciences, 27 Tai Ping Road, Beijing 100850, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Beijing Institute of Basic Medical Sciences, 27 Tai Ping Road, Beijing 100850, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Institute of Basic Medical Sciences, 27 Tai Ping Road, Beijing 100850, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wu
authors.affiliation: Beijing Institute of Basic Medical Sciences, 27 Tai Ping Road, Beijing 100850, China.
authors.forename: Zicheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, No. 316 Hospital of PLA, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Beijing Institute of Basic Medical Sciences, 27 Tai Ping Road, Beijing 100850, China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Urology, Chinese PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China. Electronic address: j_p_gao@126.com.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Gao
authors.affiliation: Beijing Institute of Basic Medical Sciences, 27 Tai Ping Road, Beijing 100850, China. Electronic address: yujyun@163.com.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D007114:Immunization; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D012093:Replicon; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D012672:Semliki forest virus / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000077022:Survivin; D016896:Treatment Outcome; D017778:Vaccines, Combined; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: C117749:Birc5 protein, mouse; D019496:Cancer Vaccines; D018997:Chorionic Gonadotropin, beta Subunit, Human; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin; D017778:Vaccines, Combined; D019444:Vaccines, DNA; D018664:Interleukin-12; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; DNA vaccine; Tumor; VEGFR2