Kang Tae Heung, Lee Jin Hyup, Song Chung Kil, Han Hee Dong, Shin Byung Cheol, Pai Sara I, Hung Chien-Fu, Trimble Cornelia, Lim Jong-Seok, Kim Tae Woo, Wu T-C
Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Gyeonggi-Do, South Korea.
Cancer Res. 2007 Jan 15;67(2):802-11. doi: 10.1158/0008-5472.CAN-06-2638.
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.
在癌症动物模型中，免疫疗法和化疗通常对小肿瘤有效。然而，这些治疗方案通常对大的、体积较大的肿瘤无效。我们发现，一种多模态治疗方案，即使用DNA疫苗接种联合化疗药物表没食子儿茶素-3-没食子酸酯（EGCG，一种存在于绿茶中的化合物），对抑制大肿瘤生长有效。研究发现，EGCG以剂量依赖的方式诱导肿瘤细胞凋亡。EGCG与DNA疫苗接种相结合导致肿瘤特异性T细胞免疫反应增强和抗肿瘤效果增强，从而产生比单独免疫疗法或EGCG更高的治愈率。此外，联合DNA疫苗接种和口服EGCG治疗为治愈的小鼠提供了长期的抗肿瘤保护。联合治疗7周后，治愈的动物排斥表达E7的肿瘤（如TC-1和B16E7）的攻击，但不排斥B16的攻击，显示出抗原特异性免疫反应。这些结果表明，多模态治疗策略，如将免疫疗法与一种杀死肿瘤的抗癌药物相结合，可能是一种比单模态治疗更有效的抗癌策略。
