Combination immunotherapy with radiation and CpG-based tumor vaccination for the eradication of radio- and immuno-resistant lung carcinoma cells

Kenji Chamoto, Tsuguhide Takeshima, Daiko Wakita, Takayuki Ohkuri, Shigeru Ashino, Tokuhiko Omatsu, Hiroki Shirato, Hidemitsu Kitamura, Yuji Togashi, Takashi Nishimura

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)934-939
Number of pages6
JournalCancer Science
Volume100
Issue number5
DOIs
StatePublished - Apr 30 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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