Class C CpG oligodeoxynucleotides as a single agent and in combination with radiotherapy efficiently delayed growth of subcutaneous B16F1 tumors.
Until now, the anti-tumor efficacy of synthetic oligodeoxynucleotides containing CpG motifs (CpG ODNs) has been reported in a number of preventive and therapeutic tumor models. Predominately class B CpG ODNs were used, relatively little has been reported regarding the class C CpG ODNs. The present study was, therefore, aimed at assessing the ability of CpG ODNs class C applied as a single agent and in combination with radiotherapy to induce the anti-tumor immunity in an experimental tumor model in mice (subcutaneous [s.c.] B16F1). Class C CpG ODNs applied three times as a single agent efficiently delayed the growth of s.c. B16F1 tumors. The combined therapy (CpG ODNs and tumor irradiation) remarkably enhanced the anti-tumor effect. The peritumoral (p.t.) application of CpG ODNs in combination with irradiation increased the number of dendritic cells (DCs) at the tumor site and improved the antigen loading and maturation of DCs. In conclusion, the combined therapy with CpG ODNs and irradiation creates a unique in situ DCs vaccine that could be easily applicable without prior knowledge of tumor antigens.
Cerkovnik
Petra
P
Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
Jezersek Novakovic
Barbara
B
Stegel
Vida
V
Novakovic
Srdjan
S
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000528:radiation effects; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D048708:Cell Growth Processes / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D005260:Female; D006801:Humans; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D011878:Radiotherapy
D000951:Antigens, Neoplasm; D051940:B7-2 Antigen; D019496:Cancer Vaccines; C527702:CpG ODN 2395; D009838:Oligodeoxyribonucleotides