We are currently developing vaccines and immunotherapeutic strategies for the prevention and treatment of human papillomavirus (HPV)-associated cervical cancer. Each year, approximately 500,000 women worldwide develop cervical cancer and 200,000 die. More than 99% of cervical cancer specimens contain HPV genomes, particularly type 16 and 18, and the viral transforming proteins, E6 and E7, are consistently expressed in cervical cancer cell lines and HPV- associated neoplasms. Thus, E6 and E7 represent true tumor-specific antigens and allow for the development of immunotherapeutic strategies to combat HPV-associated cancers.

The activity of antigen-specific T cells is known to be crucial in combating cancer. To enhance T cell-mediated immunity, we have focused on enhancing antigen processing and presentation by dendritic cells using intracellular targeting and intercellular spreading strategies. Intracellular targeting directs antigen to different subcellular locations to enhance the quality of antigen processing and presentation. Meanwhile, intercellular spreading facilitates the spread of antigen to neighboring cells by taking advantage of unique membrane translocation properties, allowing for an increase in the amount of antigen presented to effector cells. The continued development of these strategies will facilitate the development of ideal vaccines that generate a potent immune response and antitumor effect against cancer. We are also actively involved with investigating mechanisms of tumor evasion, identifying new tumor-specific antigens, and applying our vaccine strategies to other cancer systems with tumor-specific antigens (i.e. breast cancer, ovarian cancer, etc.) These endeavors are in the forefront of translational research and would be valuable to those interested in the role of viral infection, pathogenesis, molecular immunology, tumor immunology, and tumor evasion.

Pai SI, Lin YY, Macaes B, Meneshian A, Hung CF, Wu TC. (2006) Prospects of RNA interference therapy for cancer. Gene Ther. 84(6):4078-86 [PubMed]

Peng S, Trimble C, He L, Tsai YC, Lin CT, Boyd DA, Pardoll D, Hung CF, Wu TC. (2006) Characterization of HLA-A2-restricted HPV-16 E7-specific CD8(+) T-cell immune responses induced by DNA vaccines in HLA-A2 transgenic mice. Gene Ther. 100(24):13964-9 [PubMed]

Peng S, Tomson TT, Trimble C, He L, Hung CF, Wu TC. (2006) A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects. Gene Ther. 86(5):2896-909 [PubMed]

Kim TW, Lee JH, He L, Boyd DA, Hardwick JM, Hung CF, Wu TC. (2005) Modification of professional antigen-presenting cells with small interfering RNA in vivo to enhance cancer vaccine potency. Cancer Res. 144:51-74 [PubMed]

Bins AD, Jorritsma A, Wolkers MC, Hung CF, Wu TC, Schumacher TN, Haanen JB. (2005) A rapid and potent DNA vaccination strategy defined by in vivo monitoring of antigen expression. Nat. Med. 32:257-83 [PubMed]

Ellenson LH, Wu TC. (2004) Focus on endometrial and cervical cancer. Cancer Cell 7(3):239-49 [PubMed]

Kim TW, Hung CF, Boyd DA, He L, Lin CT, Kaiserman D, Bird PI, Wu TC. (2004) Enhancement of DNA vaccine potency by coadministration of a tumor antigen gene and DNA encoding serine protease inhibitor-6. Cancer Res. 6(5):472-80 [PubMed]