title: Chemotherapy enhances CD8(+) T cell-mediated antitumor immunity induced by vaccination with vaccinia virus.
abstract: The use of immunotherapy or chemotherapy alone is generally ineffective against well-established tumors. To overcome this intrinsic resistance against therapy for tumors, we have attempted to combine immunotherapy with chemotherapy. In this study, we tried to induce a rapid antitumor effect via chemoimmunotherapy using a vaccinia viral vaccine as an immunotherapeutic agent with anticancer agents including epigallocatechin-3-gallate (EGCG) and conventional anticancer drugs. Although a combination of vaccinia-mediated vaccination and chemotherapy led to a strong inhibition of tumor growth, monotherapy alone failed to completely cure tumors. In contrast, intravenous injection of cisplatin (CDDP) or cyclophosphamide (CTX) after vaccinia virus vaccination led to complete regression of the established tumors. Interestingly, anticancer drugs appear to augment the antitumor effect of the vaccinia virus-mediated immunotherapy. This effect is mainly associated with the enhanced tumor-specific CD8(+) T cell immune response induced by vaccinia virus, which was demonstrated by antibody depletion. However, anticancer drugs alone failed to induce a significant enhancement of the tumor-specific CD8(+) T cell immune response. Taken together, these results suggest that combining vaccinia virus-based immunotherapy with anticancer drugs is particularly effective against established tumors by increasing the tumor antigen-specific CD8(+) T cell immune response, which is primed by vaccinia virus-mediated vaccination.
authors.affiliation: Bioactive Molecules Delivery and Control Research Team, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, South Korea.
authors.forename: Chung Kil
authors.initials: CK
authors.lastname: Song
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Noh
authors.forename: Tae Heung
authors.initials: TH
authors.lastname: Kang
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Park
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Park
authors.forename: Byung Cheol
authors.initials: BC
authors.lastname: Shin
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002392:Catechin / Q000031:analogs & derivatives / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D052118:Lysosomal-Associated Membrane Protein 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D052118:Lysosomal-Associated Membrane Protein 1; D050725:Papillomavirus E7 Proteins; D021382:Protein Sorting Signals; D003520:Cyclophosphamide; D002392:Catechin; C045651:epigallocatechin gallate