Combination immunotherapy with radiation and CpG-based tumor vaccination for the eradication of radio- and immuno-resistant lung carcinoma cells.
Unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) is known as a ligand of toll-like receptor 9 (TLR9), which selectively activates type-1 immunity. We have already reported that the vaccination of tumor-bearing mice with liposome-CpG coencapsulated with model-tumor antigen, ovalbumin (OVA) (CpG + OVA-liposome) caused complete cure of the mice bearing OVA-expressing EG-7 lymphoma cells. However, the same therapy was not effective to eradicate Lewis lung carcinoma (LLC)-OVA-carcinoma. To overcome the refractoriness of LLC-OVA, we tried the combination therapy of radiation with CpG-based tumor vaccination. When LLC-OVA-carcinoma intradermally (i.d.) injected into C57BL/6 became palpable (7-8 mm), the mice were irradiated twice with a dose of 14 Gy at intervals of 24 h. After the second radiation, CpG + OVA-liposome was i.d. administered near the draining lymph node (DLN) of the tumor mass. The tumor growth of mice treated with radiation plus CpG + OVA-liposome was greatly inhibited and approximately 60% of mice treated were completely cured. Moreover, the combined therapy with radiation and CpG + OVA-liposome allowed the augmented induction of OVA-tetramer(+) LLC-OVA-specific cytotoxic T lymphocyte (CTL) in DLN of tumor-bearing mice. These results indicate that the combined therapy of radiation with CpG-based tumor vaccine is a useful strategy to eradicate intractable carcinoma.
Chamoto
Kenji
K
Division of Immunoregulation, Hokkaido University, Sapporo 001-0021, Japan.
Takeshima
Tsuguhide
T
Wakita
Daiko
D
Ohkuri
Takayuki
T
Ashino
Shigeru
S
Omatsu
Tokuhiko
T
Shirato
Hiroki
H
Kitamura
Hidemitsu
H
Togashi
Yuji
Y
Nishimura
Takashi
T
D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D003131:Combined Modality Therapy; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology*
C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D009838:Oligodeoxyribonucleotides