Anti-tumor effects of a human VEGFR-2-based DNA vaccine in mouse models
نویسندگان
چکیده
BACKGROUND Vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2 (Flk-1/KDR), play a key role in tumor angiogenesis. Blocking the VEGF-VEGFR-2 pathway may inhibit tumor growth. Here, we used human VEGFR-2 as a model antigen to explore the feasibility of immunotherapy with a plasmid DNA vaccine based on a xenogeneic homologue of this receptor. METHODS The protective effects and therapeutic anti-tumor immunity mediated by the DNA vaccine were investigated in mouse models. Anti-angiogenesis effects were detected by immunohistochemical staining and the alginate-encapsulate tumor cell assay. The mechanism of action of the DNA vaccine was primarily explored by detection of auto-antibodies and CTL activity. RESULTS The DNA vaccine elicited a strong, protective and therapeutic anti-tumor immunity through an anti-angiogenesis mechanism in mouse models, mediated by the stimulation of an antigen-specific response against mFlk-1. CONCLUSION Our study shows that a DNA vaccine based on a xenogeneic homologue plasmid DNA induced autoimmunity against VEGFR-2, resulting in inhibition of tumor growth. Such vaccines may be clinically relevant for cancer immunotherapy.
منابع مشابه
DNA-Based Vaccine Is More Efficient than Non-Pathogenic Live Vaccine for the Prevention of HPV16 E7-Overexpressing Cancers
Introduction: Vaccinology provides promising approaches for the control of various infectious diseases. Among different strategies, DNA vaccines offer attractive research opportunities for development of vaccines for induction of antigen-specific immunity owing to their stability, simplicity of delivery, safety and cost effectiveness. However, there is a need to increase their potency by the ...
متن کاملDetermination of Vascular Endothelial- and Fibroblast-Growth Factor Receptors in a Mouse Fibrosarcoma Tumor Model Following Photodynamic Therapy
The role of angiogenic molecules, like vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) in tumor angiogenesis was well confirmed. Photodynamic therapy (PDT) action is, to very high degree, based on tumor vasculature damage. Therefore, it seemed to be important to evaluate growth factor receptors after PDT. The extent of receptor expression was studied by immuno-histo...
متن کاملInduction of humoral immune responses and inhibition of metastasis in mice by a VEGF peptide-based vaccine
Objective(s): Blocking of vascular endothelial growth factor (VEGF) plays a pivotal role in inhibition of metastasis and is a target for development of anti-angiogenic agents. In this study, a peptide-based vaccine was designed and its potential for induction of humoral immune responses, generation of neutralizing antibodies, inhibition of tumor growth and metastasis w...
متن کاملبررسی پاسخ تکثیری لنفوسیتهای طحالی حاصل از تزریق پلاسمید کد کننده E7-HPV16 در مدل موش توموری پاپیلوماویروس
Background & Objective: Human papillomavirus (HPV) oncoproteins, including E6 and E7 are constitutively expressed in cervical cancer cells. These proteins are ideal targets to be used for developing therapeutic vaccines against existing HPV-associated carcinomas. The aim of this study was to measure the proliferation response rate of splenic lymphocytes derived from E7-HPV16 encoding plasmid in...
متن کاملPreparation and in vivo anti-tumor evaluation of human papillomavirus E7 adjuvanted with Montanide ISA 266 as a vaccine candidate
Introduction: Human papillomavirus (HPV) 16 E7 protein is expressed constitutively by HPV-infected tumor cells. Mutant versions of E7 are considered as safer candidates for immunotherapy of cervical cancer. Different strategies including formulation with adjuvants are used to induce a potent immune response against antigenic proteins. Methods: In this experimental study, we used Escherichia co...
متن کامل