HSP70 modified response against HPV based tumor

M. Farzanehpour, H. Soleimanjahi, Z.M. Hassan, A. Amanzadeh, A. Ghaemi, M. Fazeli

Department of Virology, and Department of Immunology and School of Medicine, Tarbiat Modares University, Tehran, Iran. soleim_h@modares.ac.ir

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• Immunology

BACKGROUND AND OBJECTIVES: DNA immunization is quite inventive vaccination strategies that engage the direct introduction of plasmid DNA encoding the desired antigen into the host. DNA vaccines expand strong protective responses against tumors. The desired target E7 oncogene products represent a target of choice for the therapeutic vaccination. The efficacy of vaccination is limited and it is often necessary to enhance the immune response by using adjuvant in order to achieve the desired responses. Numerous approaches have been applied to boost the effectiveness, such as the fusion or co-administration of cytokine and co-stimulatory molecules gene. Heat-shock protein 70 a family of chaperone proteins makes possible delivery of non-covalently bound peptide to MHC I molecules and influences peptide-specific CTL responses and cure treated individuals. HSP70 have been proposed as the affective adjuvant and expected to act as an appropriate substitute of both cytokine and co-stimulatory genes.

MATERIALS AND METHODS: In the current study, the impact of HSP70 co-delivery and HPV-E7 boosting on cellular immune responses and protection has been investigated by intramuscular injection of mixed DNA constructs.

RESULTS: Our results reveal that the target DNA vaccine can influence an E7-specific CTL response, which is imperative in the lysis of infected tumor cells, compared to negative control (p < 0.05). Additionally, treatment of tumor-bearing mice with pcDNA/E7 + HSP70 plasmid generates stronger immune responses and decreased significantly tumor sizes. Immunization with HSP-based vaccine with special target immunogene can induce potent and specific anti-tumor or anti-viral immune responses.

CONCLUSIONS: Co-administration of pcDNA/E7 + HSP70 plasmid was immunologically more effective than pcDNA/E7 alone. It was concluded that all the characteristics observed during our investigation demonstrate the potent adjuvant activities of HSP70 and could be an efficient approach to persuade dramatically E7-specific immune responses as future cervical cancer vaccine.

 

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