CpG oligodeoxynucleotide (ODN) is a potent enhancer of fractionated radiotherapy

Abstract

3113 Background: CpG(ODNs) are synthetic DNA sequences containing unmethylated cytosine-guanine motifs having potent immunomodulatory and antitumor effects. Based on known CpG(ODN) mechanisms and previously demonstrated in vivo radiopotentiation by bacterial immunotherapeutic agents, we tested CpG-1826 for its ability to enhance tumor response to fractionated radiotherapy. Methods: C3Hf mice bearing an immunogenic sarcoma (FSa) received single or fractionated irradiation to the tumor with or without CpG(ODN). An ODN with no CpG motif was used as an inactive control. CpG(ODN) was given sc peritumorally 3 x 100 μg per mouse at: 6mm diameter, 8mm diameter when tumors were irradiated, and 7 days later. Tumor growth delay (TGD) and tumor cure were treatment endpoints. A single radiation dose of 20 Gy or 20 Gy in 2 Gy-fractions were used. Fractionated irradiation (10 doses in 5 days) was given twice daily (6–7 h apart). Results:CpG (ODN) strongly enhanced the effect of single and fractionated radiation by factors of 2.49 and 6.91, respectively. Importantly, neither CpG (ODN) nor radiation alone produced tumor cure whereas combined treatment cured 60% for single dose and 44% for fractionated treatment. Based on these promising results we initiated full radiation dose response studies (1–9 Gy) to more accurately quantify the TCD50 (dose required to cure 50% of the tumors) in combination with CpG (ODN). Conclusions: CpG (ODN) strongly enhanced radioresponse measured by TGD and tumor cure. Therefore, CpG (ODN) may have strong potential to improve efficacy of clinical radiotherapy.