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Rongfu
Wang, PhD
Professor
Department of Immunology,
Baylor College of Medicine
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Contact Information:
rongfuw@bcm.edu
713-798-1244
Education:
Ph.D The University of Georgia
Postdoctoral Fellow Stanford University School of Medicine
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:
Paul. F. Robbins, R. F. Wang and S. A. Rosenberg. 1999. Tumor
antigens recognized by cytotoxic T lymphocytes. In ‘Cytotoxic
cells: Basic mechanisms and medical applications’, M. V. Sitkovsky
and P. Henkart, eds.
Han Ying, T. Z. Zak, R. F. Wang, K. R. Irvine, S. A. Rosenberg and N.
P. Restifo. 1999. Cancer therapy using a self-replicating RNA vaccine.
Nature Med. 5, 823-827.
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.
Wang, R.-F. 1999. Tumor antigens and their use in cancer therapy. J.
Mol. Med. 77, 640-655.
Wang, R.-F. and S. R. Rosenberg. 1999. Development of cancer vaccines
based on tumor antigens recognized by T cells. Immunol. Rev. 170, 85-100.
Zeng, G., C.E. Touloukian, X. Wang, N.P. Restifo, 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. 2001. The critical role of CD4+ T cells in antitumor immunity.
Trends in Immunology (Immunology Today), 22, 269-276.
Kershaw, M. H. C. Hsu, W. Mondesire, L. L. Parker, G. Wang, W. W. Overwijk,
R. Lapointe, J. C. Yang, R. -F. Wang, N. P. Restifo, and P. Hwu. 2001.
Immunization against endogenous retroviral tumor-associated antigens.
Cancer Res. 61, 7920-7924.
Wang, R.-F. et al. 2002. T cell responses in melanoma: implications
for immunotherapy. Critical Reviews in Oncology/Hematology, 43, 1-11.
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, R.-F. 2002. Novel strategies for enhancing antitumor immunity:
intracellular delivery of peptides and identification of MHC class II-restricted
tumor antigens. Immunological Reviews, in press.
Wang, R. F. 2002. Identification of MHC class II-restricted tumor antigens.
Methods, In press.
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. Melanoma antigens recognized by CD4+ T cells. Book
chapter. Tumor antigens recognized by T cells and antibodies, eds H.
Stauss, Y. Kawakami and G. Parmiani. Harwood Academic Publishers.
Topalian, Suzanne L., Monica I Gonzales, Yvana Ward, Xiang Wang, and R.-F. Wang. 2002. Revelation of a Cryptic MHC Class II-restricted Tumor Epitome in a Novel RNA Processing Enzyme. Cancer Res. 62, 5505-5509
Kuishin Voo, Tihui Fu, C. Rooney, H. Heslop, M. Brenner and R.-F. Wang. 2002. Identification of HLA-DP3-restricted peptides from EBNA1 recognized by CD4+ T lymphocytes. Cancer Res. 62, 7195-7199.
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. 199:459-470.
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.
Helen Y. Wang, Guangyong Peng, Zhong Guo, Ethan M. Schevach and Rong-Fu Wang. 2004. Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4 + regulatory T cells. J. Immunol. 174, 2661-2670.
Kui Shin Voo, Guangyong Peng, Zhong Guo, Tihui Fu, Yanchun Li, and Rong-Fu. Wang*. 2004. Generation and functional characterization of EBNA1-specific human CD4 + effector and regulatory T cells by in vitro stimulation with peptides. Cancer Res. 65, 1577-1586.
Wang, H.Y., Peng, G., Guo, Z., Shevach, E.M. & Wang, R.-F. 2005. Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ gegulatory T cells. J. Immunol.174, 2661-2670 .
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.
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