Chemotherapy enhances CD8(+) T cell-mediated antitumor immunity induced by vaccination with vaccinia virus.
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.
Song
Chung Kil
CK
Bioactive Molecules Delivery and Control Research Team, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, South Korea.
Han
Hee Dong
HD
Noh
Kyung Hee
KH
Kang
Tae Heung
TH
Park
Yong Sung
YS
Kim
Jin Hee
JH
Park
Eun Suk
ES
Shin
Byung Cheol
BC
Kim
Tae Woo
TW
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
D000970:Antineoplastic Agents; D052118:Lysosomal-Associated Membrane Protein 1; D050725:Papillomavirus E7 Proteins; D021382:Protein Sorting Signals; D003520:Cyclophosphamide; D002392:Catechin; C045651:epigallocatechin gallate