CpG oligodeoxynucleotides are effective in therapy of minimal residual tumour disease after chemotherapy or surgery in a murine model of MHC class I-deficient, HPV16-associated tumours.
Oligodeoxynucleotides containing guanine-cytidine dimers (CpG ODN) are potent inducers of anti-tumour immune responses. In this study, we analyzed the capacity of CpG ODN to inhibit the growth of both MHC class I-positive and -deficient tumours after debulking the tumour mass by chemotherapy or surgery. We employed an animal model resembling human papillomavirus (HPV) 16-associated tumours. Tumour cell lines with distinct cell surface expression of the MHC class I molecules were injected into syngeneic C57BL/6 mice, and the growing tumours were either subjected to cytoreductive chemotherapy with ifosfamide derivative, CBM-4A, or surgically removed. Subsequent treatment with synthetic CpG ODN significantly blocked the growth of the recurrent tumours. Our results indicate that the therapy with CpG ODN can be effective for the treatment of minimal residual tumour disease of the tumours that have escaped from the immune surveillance by downmodulating the MHC class I expression.
Reinis
Milan
M
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 6, Czech Republic.
Símová
Jana
J
Indrová
Marie
M
Bieblová
Jana
J
Bubeník
Jan
J
D000818:Animals; D045744:Cell Line, Tumor; D018899:CpG Islands; D004195:Disease Models, Animal; D005805:Genes, MHC Class I; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018365:Neoplasm, Residual / Q000188:drug therapy*; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy* / Q000821:virology*; D009841:Oligonucleotides / Q000737:chemistry / Q000627:therapeutic use*; D012008:Recurrence; D013997:Time Factors
D009841:Oligonucleotides