Research Summary
Dr. Wu’s research focuses on human papillomavirus (HPV) vaccine development.
He has created a unique preclinical murine tumor model that expresses HPV-16 oncogenic proteins (E6 and E7) and simulates specific molecular events in the progression of HPV+ precancerous lesions (CIN 3) to invasive cancer.
This model has been widely used and tested by researchers worldwide for HPV vaccine development.
Dr. Wu has focused on identifying immunotherapeutic and vaccine approaches to enhance antigen processing and presentation by dendritic cells. These include intracellular targeting and spreading strategies aimed at preventing and treating cervical lesions and cancers. Intracellular targeting directs antigens to different subcellular locations to enhance antigen processing and presentation.
Intercellular spreading helps antigens distribute to neighboring cells by taking advantage of unique intercellular transport properties that allows for an increase in the amount of antigen presented to effector cells.
Dr. Wu has created an innovative approach that combines both antigen-specific immunotherapy and anti-angiogenesis to treat HPV E7-expressing tumors.
The impressive preclinical data derived from these studies have led to several clinical trials that are either currently under way or will soon commence. The continued development of these strategies will facilitate the development of vaccines that generate a potent immune response and antitumor effect against cervical cancer.
Dr. Wu is also actively involved with investigating mechanisms of immune evasion of tumors, identifying new tumor-specific antigens and applying vaccine strategies to other cancer systems with characterized tumor-specific antigens.
Lab
The Cervical Cancer Research Lab of Drs. T-C Wu and Chien-Fu Hung has a multi-part mission to:
- Create the most effective cervical cancer vaccine for the prevention and treatment of human papillomavirus-associated malignancies
- Extend the application of the principles and strategies that we use for HPV vaccine development in order to create vaccines that target other cancers with defined tumor antigens
- Develop innovative immunological assays for human papillomavirus vaccine clinical trials
- Serve as an environment for the education of research technicians, graduate students and undergraduate students
Lab Website: Cervical Cancer Research Lab
Selected Publications
View all on PubMed
T.-C. Wu, F.G. Guarnieri, K.F. Staveley-O'Carroll, R.P. Viscidi, H.I. Levitsky, L. Hedrick, K.R. Cho, J.T. August, and D.M. Pardoll (1995) Engineering a novel pathway for MHC Class II Presentation of Antigens. Proc. Natl. Acad. Sci. 92: 11671-11675.
K.-Y. Lin, F. G. Guarnieri, K. F. Staveley-O'Carroll, H. I. Levitsky, J. T. August, D. M. Pardoll and T.-C. Wu (1996) Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Research 56:21-26.
C.-H. Chen, T.-L. Wang, C.-F. Hung, Y. Yang, H. Chen, R. A. Young, D. M. Pardoll and T.-C. Wu (2000) Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene. Cancer Research, 60:1035-1042.
W.-F. Cheng, C.-F. Hung, C.-Y. Chai, K.-F. Hsu, L. He, M. Ling and T.-C. Wu (2001) Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen. J. Clin. Invest. 108: 669-78.
T. W. Kim, C.-F. Hung, M. Ling, J. Juang, L. He, J. M. Hardwick, S. Kumar, and T.-C. Wu (2003) Enhancing DNA vaccine potency by co-administration of DNA encoding anti-apoptotic proteins. J. Clin. Invest. 112: 109-117.
C. L. Trimble, S. Peng, F. Kos, P. Gravitt, R. Viscidi, E. Sugar, D. Pardoll, T.-C. Wu (2009) A phase I trial of a HPV DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clinical Cancer Research 15(1):361-7.
K. H. Noh, B. W. Kim, K.-H. Song, H. Cho, Y.-H. Lee, J. H. Kim, H. Cho, J.-Y. Chung, J.-H. Kim, S. M. Hewitt, S.-Y. Seong, C.-P. Mao, T-C Wu* and T. W. Kim* (2012) Nanog signaling in cancer promotes stem-like phenotype and immune evasion. J. Clin. Invest. 122: 4077-4093 * Co-corresponding authors.
T.H. Kang,CP Mao, SY Lee, A Chen, JH Lee, T.W. Kim, R Alvarez, RB Roden, D Pardoll, CF Hung, T.-C. Wu (2013). Chemotherapy acts as an adjuvant to convert the tumor microenvironment into a highly permissive state for vaccination-induced antitumor immunity. Cancer Research. 73(8);2493-2504.
L. Maldonado, JE Teague, MP Morrow, I. Jotova , T.-C. Wu, C. Wang, C. Desmarais, JD Boyer, B. Tycko, HS Robins, RA Clark, CL Trimble. (2014) Intramuscular therapeutic vaccination targeting HPV16 induces T cell responses that localize in mucosal lesions. Sci Transl Med. 29 (6) 221.
Y Sun, S Peng, J Qiu, J Miao, B Yang, J Jeang, CF Hung, T.-C. Wu (2015) Intravaginal HPV DNA vaccination with electroporation induces local CD8+ T-cell immune responses and antitumor effects against cervicovaginal tumors. Gene Therapy advance online publication. 22 (7): 528-535
Patents
DNA Vaccine Enhancement with MHC Class II Activators
Patent # US9085638 B2 | 2015
RNA Interference That Blocks Expression of Pro-Apoptotic Proteins Potentiates Immunity Induced by DNA and Transfected Dendritic Cell Vaccines
Patent # US9011866 B2 | 2015
Nucleic Acid Immunogenic Compositions Encoding Hsp-antigen Chimera
Patent # CA2388045 C | 2014
Superior Molecular Vaccine Linking the Translocation Domain of a Bacterial Toxin to an Antigen
Patent # US8128922 B2 | 2012
Molecular Vaccine Linking an Endoplasmic Reticulum Chaperone Polypeptide to an Antigen
Patent # US8007781 B2 | 2011
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