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Research Outline
Hydrogel-based cytokine carrier for oral cancer therapy
Despite aggressive multimodality treatments for oral carcinoma,
most tumors have local or even regional recurrences. Our study is
to establish a novel topical immunotherapy for ORAL CANCER that
can be applied to affected surfaces without systemic toxicity.
Our approach will use a hydrogel mediated release of pro-inflammatory
cytokines into the tumor microenvironment. The potent anti-tumoral
effects of cytokines in a local region will mobilize tumor associated
lymphocytes that can eradicate tumor cells. The essential criteria
for the proposed administration lie in controlling dosage, establishing
release kinetics and preserving cytokine bioactivity. The anti-tumor
efficacy of a biodegradable hydrogel mediated delivery of IL-12
alone or its synergistic combination will be optimized in chimeric
human/SCID mouse model of oral cancer before clinical application
in Phase I studies.
This study may serve as a basis for future studies on anti-tumor
mechanisms and the search for other agents that can be used by the
method in various approachable solid tumors.
Faculty
Fang-An Chen Ph.D, M.D.
Zhi-Ming He
Education
The laboratory of Head and Neck Oncology welcomes Medical Students
and Residents interested in pursuing short term or long term projects
in oncology research.
Publications
1. Zylstra, S., F.A. Chen, S.K. Ghosh, E.A. Repasky, U. Rao, H.
Takita, and R.B. Bankert, Membrane-associated glycoprotein (gp 160)
identified on human lung tumors by a monoclonal antibody. Cancer
Research, 1986. 46(12 Pt 1): p. 6446-51.
2. Sugiyama, Y., F.A. Chen, H. Takita, and R.B. Bankert, Selective
growth inhibition of human lung cancer cell lines bearing a surface
glycoprotein gp160 by 125I-labeled anti-gp160 monoclonal antibody
[see comments]. Cancer Research, 1988. 48(10): p. 2768-73.
3. Bankert, R.B., T. Umemoto, Y. Sugiyama, F.A. Chen, E. Repasky,
and S. Yokota, Human lung tumors, patients' peripheral blood lymphocytes
and tumor infiltrating lymphocytes propagated in scid mice. Current
Topics in Microbiology & Immunology, 1989. 152: p. 201-10.
4. Chen, F.A., E.A. Repasky, H. Takita, B.S. Schepart, and R.B.
Bankert, Cell surface glycoprotein associated with human lung tumors
that is similar to but distinct from the epidermal growth factor
receptor. Cancer Research, 1989. 49(13): p. 3642-9.
5. Chen, F.A., E.A. Repasky, and R.B. Bankert, Human lung tumor-associated
antigen identified as an extracellular matrix adhesion molecule.
Journal of Experimental Medicine, 1991. 173(5): p. 1111-9.
6. Chen, F.A., T. Alosco, B.A. Croy, K. Narumi, D.H. Percy, and
R.B. Bankert, Clones of tumor cells derived from a single primary
human lung tumor reveal different patterns of beta 1 integrin expression.
Cell Adhesion & Communication, 1994. 2(4): p. 345-57.
7. Narumi, K., F.A. Chen, R.B. Bankert, and H. Takita, Generation
of monoclonal antibodies that distinguish between mesotheliomas
and other tumor of the lung. Nippon Geka Hokan - Archiv fur Japanische
Chirurgie, 1994. 63(4): p. 129-38.
8. Chen, F.A., S.S. Williams, W.C. Fanslow, and R.B. Bankert, Human
antibody response in human peripheral blood leukocyte/severe combined
immunodeficient chimeric model is dependent on B and T cell costimulation
via CD40/CD40 ligand. Journal of Immunology, 1995. 155(6): p. 2833-40.
9. Sakakibara, T., F.A. Chen, H. Kida, K. Kunieda, R.E. Cuenca,
F.J. Martin, and R.B. Bankert, Doxorubicin encapsulated in sterically
stabilized liposomes is superior to free drug or drug-containing
conventional liposomes at suppressing growth and metastases of human
lung tumor xenografts. Cancer Research, 1996. 56(16): p. 3743-6.
10. Sakakibara, T., Y. Xu, H.L. Bumpers, F.A. Chen, R.B. Bankert,
M.A. Arredondo, S.B. Edge, and E.A. Repasky, Growth and metastasis
of surgical specimens of human breast carcinomas in SCID mice. The
Cancer Journal from Scientific American, 1996. 2(5): p. 291-300.
11. Williams, S.S., F.A. Chen, H. Kida, S. Yokata, K. Miya, M. Kato,
M.P. Barcos, H.Q. Wang, T. Alosco, T. Umemoto, B.A. Croy, E.A. Repasky,
and R.B. Bankert, Engraftment of human tumor-infiltrating lymphocytes
and the production of anti-tumor antibodies in SCID mice. Journal
of Immunology, 1996. 156(5): p. 1908-15.
12. Iwanuma, Y., F.A. Chen, N.K. Egilmez, H. Takita, and R.B. Bankert,
Antitumor immune response of human peripheral blood lymphocytes
coengrafted with tumor into severe combined immunodeficient mice.
Cancer Research, 1997. 57(14): p. 2937-42.
13. Egilmez, N.K., Y.S. Jong, Y. Iwanuma, J.S. Jacob, C.A. Santos,
F.A. Chen, E. Mathiowitz, and R.B. Bankert, Cytokine immunotherapy
of cancer with controlled release biodegradable microspheres in
a human tumor xenograft/SCID mouse model. Cancer Immunology, Immunotherapy,
1998. 46(1): p. 21-4.
14. Bankert, R.B., F.A. Chen, Y. Sugiyama, and N. Egilmez, Patient
immune response to tumors monitored using SCID mouse models. [Review]
Immunological Investigations, 2000. 29(2): p. 171-6.
15. Conway, T.F.J., M.S. Sabel, M. Sugano, J.G. Frelinger, N.K.
Egilmez, F.A. Chen, and R.B. Bankert, Growth of human tumor xenografts
in SCID mice quantified using an immunoassay for tumor marker protein
in serum. Journal of Immunological Methods, 2000. 233(1-2): p. 57-65.
16. Kuriakose, M.A., F.A. Chen, N.K. Egilmez, Y.S. Jong, E. Mathiowitz,
M.D. DeLacure, W.L. Hicks, Jr., T.L. Loree, and R.B. Bankert, Interleukin-12
delivered by biodegradable microspheres promotes the antitumor activity
of human peripheral blood lymphocytes in a human head and neck tumor
xenograft/SCID mouse model. Head & Neck, 2000. 22(1): p. 57-63.
17. Sabel, M.S., T.F. Conway, F.A. Chen, and R.B. Bankert, Monoclonal
antibodies directed against the T-cell activation molecule CD137
(interleukin-A or 4-1BB) block human lymphocyte-mediated suppression
of tumor xenografts in severe combined immunodeficient mice. Journal
of Immunotherapy, 2000. 23(3): p. 362-8.
18. Sabel, M.S., M. Yamada, Y. Kawaguchi, F.A. Chen, H. Takita,
and R.B. Bankert, CD40 expression on human lung cancer correlates
with metastatic spread. Cancer Immunology, Immunotherapy, 2000.
49(2): p. 101-8.
19. Sugano, M., N.K. Egilmez, S.J. Yokota, F.A. Chen, J. Harding,
S.K. Huang, and R.B. Bankert, Antibody targeting of doxorubicin-loaded
liposomes suppresses the growth and metastatic spread of established
human lung tumor xenografts in severe combined immunodeficient mice.
Cancer Research, 2000. 60(24): p. 6942-9.
20. Yamada, M., T. Shiroko, Y. Kawaguchi, Y. Sugiyama, N.K. Egilmez,
F.A. Chen, and R.B. Bankert, CD40-CD40 ligand (CD154) engagement
is required but not sufficient for modulating MHC class I, ICAM-1
and Fas expression and proliferation of human non-small cell lung
tumors. International Journal of Cancer, 2001. 92(4): p. 589-99.
21. Sugano M. Conway TF Jr. Kelleher RJ Jr. Sugiyama Y. Chen FA.
Bankert RB. Bernstein SH. Human dendritic cells pulsed with autologous
Epstein-Barr virus transformed B-cell lymphoblastoid cell (BCL)
lysate elicit a BCL specific MHC-class II restricted T-cell response.
Journal of Experimental & Clinical Cancer Research. 2001. 20(2):175-82
22. Sugiyama, Y., M. Kato, F.A. Chen, S.S. Williams, Y. Kawaguchi,
K. Miya, Y.S. Jong, E. Mathiowitz, N.K. Egilmez, and R.B. Bankert,
Human inflammatory cells within the tumor microenvironment of lung
tumor xenografts mediate tumor growth suppression in situ that depends
on and is augmented by interleukin-12. Journal of Immunotherapy,
2001. 24(1): p. 37-45.
23. Egilmez, N.K., S.D. Hess, F.A. Chen, H. Takita T.F. Conway and
R.B. Bankert, Human CD4+ effector T-cells mediate an indirect IL-12
and IFN? dependent suppression of autologous HLA-negative lung tumor
xenografts in SCID mice. Cancer Research. 2002. 62(9):2611-7
24. Chen, F.A., M.A. Kuriakose, M.X. Zhou, M.D. DeLacure and R.L.
Dunn. Feasibility of biodegradable polymer mediated delivery of
cisplatin for the treatment of head and neck squamous cell carcinoma
in a chimeric mouse model. Head and Neck. 2003. 25:554-60
25. Sok, J, M.A. Kuriakose, V.B. Mahajan, A.L. Pearlman, M.D. DeLacure,
and F.A. Chen. Tissue-specific gene expression of head and neck
squamous cell carcinoma in vivo by complementary DNA microarray
analysis. Arch Otolaryngol Head Neck Surg. 2003. 129:760-70
26. M.A. Kuriakose1, W.T. Chen2, Z.M. He1, A. Sikora1, P. Zhang2,
F. Hsu3, M.D. Delacure1, Z.Y. Zhang2, F.A. Chen1. Selection and
validation of differentially expressed genes in head and neck cancers.
Cellular and Molecular Life Science. 2004. 61(11):1372-83
27. H.Y. Chuang, H, Liu, F.A. Chen, C.Y. Kao, and D.F. Hsu. Combination
methods in microarray analysis. Proceedings of the 7th International
Symposium on Parallel Architectures, Algorithms and Networks. 2004.
IEEF Computer Society Press, Los Alamitos, USA. P 625-630
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