Successful treatment of intracranial gliomas in rat by oligodeoxynucleotides containing CpG motifs.
Phosphorothioate oligodeoxynucleotides with CpG motifs (CpG-ODNs) activate various immune cell subsets and induce production of numerous cytokines. To evaluate whether CpG-ODNs can induce rejection of established tumors, Lewis rats were inoculated intracerebrally with syngeneic CNS-1 glioma cells and subsequently injected with CpG-ODNs into the tumor bed. Although all of the control rats (n = 14) died within 23 days, 88% of the animals (n = 8) treated with a single CpG-ODN injection 5 days after tumor inoculation showed long-term survival (>90 days; P < 0.002). CpG-ODNs increased tumoral infiltration with macrophage/microglial cells, CD8, and natural killer lymphocytes. CpG-ODN-cured animals were further protected against a second tumor challenge. CpG-ODNs had no effect on a s.c. CNS1 tumor in nude mice, which suggested that CpG-ODN is not directly cytotoxic and that immunostimulation is required for the antitumoral effect. These findings suggest that intratumoral injections of CpG-ODNs represent a new immunotherapeutic approach in human gliomas, which overcome the need for the selection and purification of a tumoral antigen.
Carpentier
A F
AF
Biologie des Interactions Neurones/Glie, Institut National de la Santé et de la Recherche Médicale U-495, Université Pierre Marie Curie, and Fédération de neurologie Mazarin, Paris, France. antoine.carpentier@psl.ap-hop-paris.fr
Xie
J
J
Mokhtari
K
K
Delattre
J Y
JY
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D016827:CD8 Antigens / Q000378:metabolism; D019496:Cancer Vaccines / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D017628:Microglia / Q000378:metabolism; D009368:Neoplasm Transplantation; D009841:Oligonucleotides / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016827:CD8 Antigens; D019496:Cancer Vaccines; D009841:Oligonucleotides