Si-Yi Chen, M.D., Ph.D. - Faculty
Adjunct Faculty, Center for Cell and Gene Therapy, Departments of Molecular and Human Genetics, and Pathology & Immunology
Professor, University of Southern California
M.D., The Second Medical College, Shanghai, 1983
Ph.D., National Academy of Medical Sciences of China, 1988
Postdoc, University of Alabama at Birmingham, 1989
Postdoc, Dana-Farber Cancer Institute, Harvard Medical School, 1992
Gene therapy and antigen presentation for vaccine development. Gene therapy for cancer and AIDS
Research in the laboratory is directed toward developing genetic technologies for cancer and AIDS therapy. Several technologies have been developed, including immunotoxin-producing cell, intrabody, and intrakine technologies. The immunotoxin-producing cell technology utilizes the antibody specificity, toxin potency, and effector-cell-properties of lymphocytes to kill target cells. Lymphocytes were transduced to produce and secrete immunotoxins (as toxin carrier and producer) and shown to have potent and selective cytotoxicity to tumors. In future, we will further develop and improve this novel strategy for treatment of cancer, such as, breast, ovarian and brain tumors.
The intrabody technology was developed by expressing engineered antibodies to inactivate intracellular proteins. Intrabody provides a powerful new approach to molecularly dissect functions of target proteins and can also be used as a new class of therapeutic molecules for gene therapy. Currently, a study is underway to determine whether cyclin E, which is overexpressed in breast cancer cells plays a critical role in establishing and maintaining the transformed phenotype of cancer cells. Moreover, an intrakine technology was developed to inactivate cell surface receptors. For example, intrakines can be used to effectively inactivate chemokine receptors to protect T-cells from HIV infection. We are currently evaluating whether intrakine can be used to modify T-cells and stem cells for HIV-1 therapy in animal models and clinical trials.
Antigen presentation for immunotherapy and vaccine development
The laboratory also develops technologies to enhance antigen presentation for inducing potent and broad immune responses. A retrogen approach was developed by using a unifying antigen presentation mechanism to induce T-cell and B-cell responses. For example, dendritic cells can be transduced to produce and secrete a retrogen consisting of an antigen fused with a cell-binding domain and to process the retrogen as an exogenous antigen after receptor-mediated internalization for major histocompatibility complexes (MHC)-class -I and -II presentation. This technology may provide a powerful and generic means to develop potent vaccines and immunotherapies. Currently, we are improving and using the retrogen technology for developing AIDS and tumor vaccines.
- Marasco, W.A. Haseltine, W.A. and S.-Y. Chen. 1993. Design, intracellular expression, and activity of a human anti-HIV-1 gp120 single chain antibody. Proc. Natl. Acad. Sci. USA. 90:7889-7893.
- Chen, S.-Y. A. Yang, J. Chen, T. Kute, R. King, Y. Cong, C. Yao, and X. Huang. 1997. Potent anti-tumor activities of a new class of tumor-specific cytotoxic cells. Nature 385:78-80.
- Yang. A. and S.-Y. Chen. 1997. A new class of antigen-specific cytotoxic cells. Nature Biotech. 15, 46-51.
- Yang, A., X., Bai, J. Chen, X. Huang, and S.-Y. Chen. 1997. Phenotypic knock-out HIV-1 chemokine co-receptor CCR5 by intrakine as potential therapeutic approach. Proc. Natl. Acad. Sci. USA. 94:11567-11572.
- Chen, J., A. Yang, X. Bai, Y. Cong, Y. and S.-Y. Chen. 1997. Inactivation of HIV-1 chemokine co-receptor CXR4 by a novel intrakine strategy. Nature Medicine. 3:1110-1116.
- Chen, S.-Y. Intrabody and Immunotoxin-Producing Cell Approaches for Cancer Gene Therapy. Cancer Gene Therapy, W.B. Saunders, Philadelphia, PA, 1998.
To see a complete list of Dr. Chen's publications, visit