Photodynamic therapy-generated tumor cell lysates with CpG-oligodeoxynucleotide enhance immunotherapy efficacy in human papillomavirus 16 (E6/E7) immortalized tumor cells.
Immunotherapy with photodynamic therapy (PDT) offers great promise as a new alternative for cancer treatment; however, its use remains experimental. In this study, we examined the immunotherapeutic significance of human papillomavirus (HPV)-immortalized tumor cell lysates induced by PDT with CpG-oligodeoxynucleotide (ODN). PDT-cell lysates were generated by irradiating Radachlorin (5 microg/mL) preloaded TC-1 cells carrying HPV 16 E7. PDT-cell lysates plus ODN coinjection for protection against E7-expressing tumors as well as specific immune responses were evaluated with the following tests: heat shock protein 70 (HSP70) enzyme-linked immunosorbent assay, in vitro and in vivo tumor growth inhibition, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) assay, cytotoxic T-lymphocyte assay, and fluorescence activated cell sorting (FACS) analysis. PDT-cell lysates plus ODN coinjection showed a significant suppression of tumor growth at both prophylactic and therapeutic levels, compared to PDT (or F/T)-cell lysates or ODN alone. In addition, we evaluated the level of the immune response with the coinjection. HSP70, an important regulator of inflammatory and immune response, was observed in abundance in the PDT-cell lysates. IFN-gamma production and cytotoxic T lymphocytes (CTL) responses were induced by PDT-cell lysates plus ODN injection. The coinjection resulted in PDT-cell lysate-specific antibodies (IgG1, IgG2a, IgG2b, and IgG3) and T-helper cell responses significantly higher than PDT-cell lysates alone. Moreover, IFN-gamma production and CTL responses were significantly induced in the PDT-cell lysate plus ODN immunized groups. These enhanced immune responses appeared to be mediated by CD8+ T cells only. These data suggest that PDT-cell lysates plus ODN injection may be an effective approach to induce CTL immune responses as a possible immunotherapeutic strategy for cancer therapy.
Bae
Su-Mi
SM
Cancer Research Institute, The Catholic University of Korea, Seoul 137-040, Korea.
Kim
Yong-Wan
YW
Kwak
Sun-Young
SY
Kim
Yong-Wook
YW
Ro
Duck-Yeong
DY
Shin
Jong-Chul
JC
Park
Choong-Hak
CH
Han
Sei-Jun
SJ
Oh
Chung-Hun
CH
Kim
Chong-Kook
CK
Ahn
Woong-Shick
WS
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use; D002457:Cell Extracts / Q000528:radiation effects / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D010778:Photochemotherapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D002457:Cell Extracts; D050884:HSP72 Heat-Shock Proteins; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma