Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
권호 표지

DNA vaccines for cervical cancer: from bench to bedside

Hung, Chien-Fu;Monie, Archana;Alvarez, Ronald D.;Wu, T.C.

  • Published : 20071200
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Abstract

ciated with human papillomaviruses (HPVs), partic-ularly HPV type 16. The clear association between HPV infection and cervical cancer indicates that HPV serves as an ideal target for development of preventive and therapeutic vaccines. Although the recently licensed preventive HPV vaccine, Gardasil, has been shown to be safe and capable of generating significant pro-tection against specific HPV types, it does not have therapeutic effect against established HPV infections teins, E6 and E7, are consistently co-expressed in HPV-expressing cervical cancers and are important in the induction and maintenance of cellular transforma-tion. Therefore, imunotherapy targeting E6 and/or E7 proteins may provide an opportunity to prevent and treat HPV-associated cervical malignancies. It has been established that T cel-mediated imunity is one of the most crucial components to defend against HPV infections and HPV-associated lesions. Therefore, ef-fective therapeutic HPV vaccines should generate ponses. DNA vaccines have emerged as an atractive approach for antigen-specific T cell-mediated im-munotherapy to combat cancers. Intradermal admin-istration of DNA vacines via a gene gun represents an efficient way to deliver DNA vaccines into professional antigen-presenting cells in vivo. Professional anti-gen-presenting cells, such as dendritic cells, are the most efective cells for priming antigen-specific T cells. Using the gene gun delivery system, we tested ing strategies for enhancing MHC class I and class II presentation of encoded model antigen HPV-16 E7. Furthermore, we have developed a strategy to prolong the life of DCs to enhance DNA vaccine potency. More recently, we have developed a strategy to generate an-tigen-specific CD4+T cell imune responses to further enhance DNA vaccine potency. The impressive pre- clinical data generated from our studies have led to several HPV DNA vaccine clinical trials.

Keywords

References

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