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Epigallocatechin-3-Gallate Enhances CD8⁺ T Cell–Mediated Antitumor Immunity Induced by DNA Vaccination

¹ Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Gyeonggi-Do, South Korea; ² Department of Advanced Materials, Korea Research Institute of Chemical Technology, Daejeon, South Korea; Departments of ³ Pathology, ⁴ Obstetrics and Gynecology, ⁵ Oncology, ⁶ Molecular Microbiology and Immunology, and ⁷ Otolaryngology/Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland; and ⁸ Research Center for Women's Diseases, Sookmyung Women's University, Seoul, South Korea

Requests for reprints: Tae Woo Kim, Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, 516 Gojan-1 Dong, Ansan-Si, Gyeonggi-Do 425-707, South Korea. Phone: 82-31-412-6713; Fax: 82-31-412-6718; E-mail: twkim0421{at}korea.com and T-C. Wu, Departments of Pathology, Johns Hopkins University School of Medicine, CRBII, 1550 Orleans Street, Baltimore, MD 21231. Phone: 410-614-3899; Fax: 443-287-4295; E-mail: wutc{at}jhmi.edu.

Immunotherapy and chemotherapy are generally effective against small tumors in animal models of cancer. However, these treatment regimens are generally ineffective against large, bulky tumors. We have found that a multimodality treatment regimen using DNA vaccination in combination with chemotherapeutic agent epigallocatechin-3-gallate (EGCG), a compound found in green tea, is effective in inhibiting large tumor growth. EGCG was found to induce tumor cellular apoptosis in a dose-dependent manner. The combination of EGCG and DNA vaccination led to an enhanced tumor-specific T-cell immune response and enhanced antitumor effects, resulting in a higher cure rate than either immunotherapy or EGCG alone. In addition, combined DNA vaccination and oral EGCG treatment provided long-term antitumor protection in cured mice. Cured animals rejected a challenge of E7-expressing tumors, such as TC-1 and B16E7, but not a challenge of B16 7 weeks after the combined treatment, showing antigen-specific immune responses. These results suggest that multimodality treatment strategies, such as combining immunotherapy with a tumor-killing cancer drug, may be a more effective anticancer strategy than single-modality treatments. [Cancer Res 2007;67(2):802–11]

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