Epigallocatechin-3-gallate enhances CD8+ T cell-mediated antitumor immunity induced by DNA vaccination.
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.
Kang
Tae Heung
TH
Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Gyeonggi-Do, South Korea.
Lee
Jin Hyup
JH
Song
Chung Kil
CK
Han
Hee Dong
HD
Shin
Byung Cheol
BC
Pai
Sara I
SI
Hung
Chien-Fu
CF
Trimble
Cornelia
C
Lim
Jong-Seok
JS
Kim
Tae Woo
TW
Wu
T-C
TC
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002392:Catechin / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology / Q000628:therapy* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D002392:Catechin; C045651:epigallocatechin gallate