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Immunology

Houston, Texas

Immunology lab with students
Department of Immunology
not shown on screen

Rongfu Wang, Ph.D.

Rongfu Wang photoProfessor, Department of Immunology and The Center for Cell and Gene Therapy

Ph. D., University of Georgia
Postdoctoral fellow, Stanford University

E-mail: rongfuw@bcm.edu

Research interests:
Tumor antigens, cancer vaccine development and the mechanism of self tolerance

Our research interests include the molecular mechanism of T cell mediated tumor immunity and self-tolerance. It is well known that T cells play an important role in the inhibition of tumor growth and tumor destruction. To understand the molecular basis of tumor immunity, we are interested in identifying tumor rejection antigens recognized by CD4+ and CD8+ T cells. Identification of these tumor rejection antigens has provided new opportunities for the development of effective cancer vaccines and for studying the mechanism of T cell mediated tumor immunity and autoimmunity. Specifically, we are currently working on the following projects:

1. Identification of MHC class II-restricted tumor antigens and their role in tumor immunity. In the last few years, a number of MHC class I-restricted tumor antigens have been identified in melanoma and other cancers. Clinical studies using these antigens showed some evidence of therapeutic effect on inhibiting tumor growth, but these immune responses are weak and transient. One possible explanation is that optimal anti-tumor immunity requires the participation of CD4+ and CD8+ T cells since CD4+ T cells play a central role in initiating and maintaining host immune responses against cancer. To this end, we recently developed a novel approach for the identification of MHC class II-restricted tumor antigens recognized by CD4+ T cells. A number of tumor reactive CD4+ T cell lines have been generated. Therefore, we are currently addressing the question of what kinds of tumor antigens are recognized by these CD4+ T cells.

2. Animal tumor models and cancer vaccines. To evaluate the role of MHC class II-restricted tumor antigens and CD4+ T cells, we are investigating CD4+ and CD8+ T cell responses using DR-transgenic mice. Dendritic cells pulsed with peptides or infected with adenovirus encoding tumor antigens are being used to immunize mice. One important aspect of investigation is to understand the mechanism of how to break self-tolerance and direct immune responses against cancer, but not normal tissues. T cell activation and apoptosis are also investigated in animal tumor models. These studies will ultimately lead to the development of more effective cancer vaccinces.

3. The use of microarray technology for the identification Tumor-specific antigens. Although T cell defined tumor antigens have been identified in melanoma and a few other tumors, it has been difficult to tumor reactive T cells thus far. We are using a microarray technology to identify tumor specific antigens in prostate and breast cancers, which are expressed only in tumor cells, but not in normal cells. Their role in tumorigenesis and immunogenecity are being evaluated.

Selected Publications:

  • Wang, R. F., X. Wang and S. A. Rosenberg. 1999. Identification of a novel MHC class-II-restricted tumor antigen resulting from a chromosomal rearrangement recognized by CD4+ T cells. J. Exp. Med. 189, 1659-1668.

  • Wang, R. F., X. Wang, A. L. Atwood, S. L. Topalian and S.A. Rosenberg. 1999. Cloning genes encoding MHC class II-restricted antigens: mutated human CDC27 as a tumor antigen. Science 284, 1351-1354.

  • Zeng, G., C. Touloukian, N. P. Nestifo, S. A. Rosenberg and R. F. Wang. 2000. Identification of CD4+ T cell epitopes from NY-ESO-1 presented by HLA-DR molecules. J. Immunol. 165: 1153-1159

  • Zeng, G., X. Wang, P. F. Robbins, S.A. Rosenberg, and R.-F. Wang. 2001. Identification of DP4 restricted T cell epitopes from NY-ESO-1: its association with antibody response. PNAS, 98, 3964-3969.

  • Wang, R.-F and H. Y. Wang. 2002. Enhancement of antitumor immunity by prolonging antigen presentation on dendritic cells. Nature Biotechnology. 20: 149-154.

  • Wang, H. Y., J. Zhou, K. Zhou, F. M. Marincola, and R. F. Wang. 2002. Identification of a mutated fibronection as a tumor antigen recognized by CD4+ T cells: its role in extracellular matrix formation and tumor metastasis. J. Exp. Med 195: 1397-1406.

  • Helen Y. Wang, Tihui Fu, Gang Wang, Gang, Zeng, Donna, M. Perry-Lalley, James C. Yang, Nicholas P. Restifo, Patrick Hwu, and R.-F. Wang. 2002. TAT-mediated tumor antigen delivery into dendritic cells for generating CD4+ T cells-dependent antitumor immunity. J. Clinical Investigation 109: 1463-1470

  • Wang, R.-F. 2002. Novel strategies for enhancing antitumor immunity: intracellular delivery of peptides and identification of MHC class II-restricted tumor antigens. Immunol Reviews 188, 65-80.

  • Kui Shin Voo, Tihui Fu, Helen Y. Wang, Helen E. Heslop, Malcolm K. Brenner, Cliona M. Rooney, and R.-F. Wang. 2004. Evidence for the presentation of MHC class I-restricted EBNA1 peptides to CD8+ T lymphocytes. J. Exp. Med. 199:1-13.

  • Helen Y. Wang, Dean A. Lee, Zhong Guo, Guangyong Peng, Hoainam T. Nguyen-Jackson, Ethan M. Shevach and Rong-Fu Wang. 2004. Tumor-specific human CD4+ regulatory T cells and their ligands: implication for immunotherapy. Immunity 20:107-118.

  • Tihui Fu, Kuishin Voo and Rong-Fu Wang. 2004. The critical role of EBNA1-specific CD4+ T cells in controlling tumor growth in a new murine Burkitt Lymphoma model. J. Clinical Investigation, 114:542-550.

  • Wang, H.Y. & Wang, R.F. 2005. Antigen-specific CD4(+) regulatory T cells in cancer: implications for immunotherapy. Microbes Infect 7, 1056-1062.

  • Voo, K.S. G. Peng, Z. Guo, T. Fu, Y. Li, L. Frappier and R. F. Wang. 2005. Functional characterization of EBV-encoded nuclear antigen 1-specific CD4+ helper and regulatory T cells elicited by in vitro peptide stimulation. Cancer Res 65, 1577-86.

  • Peng, G. Z. Guo, Y. Kiniwa. K.S. Voo, W. Peng, T. Fu, D. Y. Wang,, Y. Li, H. Y. Wang and R. F. Wang. 2005 Toll-like receptor 8 mediated-reversal of CD4+ regulatory T cell function. Science 309, 1380-1384.

    For a complete list of Dr. Wang's publications, visit PubMed.

Contact Information:
    Rongfu Wang, Ph.D.
    Department of Immunology
    Center for Cell and Gene Therapy
    ALKEK Building N1120
    One Baylor Plaza
    Houston, Texas 77030
Pone: 713-798-1244
Fax: 713-798-1263
E-mail: rongfuw@bcm.edu

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