Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma 1

Oligodeoxynucleotides containing CpG motifs (CpG ODNs) display a strong immunostimulating activity and drive the immune response toward the Th1 (T helper type 1) phenotype. These ODNs have shown promising efficacy in preclinical studies when injected locally in several cancer models. We conducted a phase 1 trial to define the safety profile of CpG-28, a phosphorothioate CpG ODN, administered intratumorally by convection-enhanced delivery in patients with recurrent glioblastoma. Cohorts of three to six patients were treated with escalating doses of CpG-28 (0.5–20 mg), and patients were observed for at least four months. Twenty-four patients entered the trial. All patients had previously been treated with radiotherapy, and most patients had received one or several types of chemotherapy. Median

[1]  Lin Chen,et al.  Successful combination of local CpG‐ODN and radiotherapy in malignant glioma , 2005, International journal of cancer.

[2]  C. Cooper,et al.  CPG 7909, an Immunostimulatory TLR9 Agonist Oligodeoxynucleotide, as Adjuvant to Engerix-B® HBV Vaccine in Healthy Adults: A Double-Blind Phase I/II Study , 2004, Journal of Clinical Immunology.

[3]  Y. Li,et al.  Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine. , 2004, Vaccine.

[4]  D. Klinman.  Use of CpG oligodeoxynucleotides as immunoprotective agents , 2004, Expert opinion on biological therapy.

[5]  Stephanie B. Conant,et al.  Autoreactive T Cells Persist in Rats Protected against Experimental Autoimmune Encephalomyelitis and Can Be Activated through Stimulation of Innate Immunity1 , 2004, The Journal of Immunology.

[6]  D. Groothuis,et al.  Comparative pharmacokinetics of 14C-sucrose in RG-2 rat gliomas after intravenous and convection-enhanced delivery. , 2004, Neuro-oncology.

[7]  A. Krieg.  Antitumor applications of stimulating toll-like receptor 9 with CpG oligodeoxynucleotides , 2004, Current oncology reports.

[8]  Harald Neumann,et al.  Neuronal injury mediated via stimulation of microglial toll‐like receptor‐9 (TLR9) , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[9]  S. Halperin,et al.  A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant. , 2003, Vaccine.

[10]  J. Delattre,et al.  CpG-oligonucleotides for cancer immunotherapy : review of the literature and potential applications in malignant glioma. , 2003, Frontiers in bioscience : a journal and virtual library.

[11]  M Brada,et al.  Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[12]  D. Osoba,et al.  A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse , 2000, British Journal of Cancer.

[13]  K. Mokhtari,et al.  Successful treatment of intracranial gliomas in rat by oligodeoxynucleotides containing CpG motifs. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[14]  Lin Chen,et al.  Oligodeoxynucleotides containing CpG motifs can induce rejection of a neuroblastoma in mice. , 1999, Cancer research.

[15]  G T Gillies,et al.  Distribution and stability of antisense phosphorothioate oligonucleotides in rodent brain following direct intraparenchymal controlled-rate infusion. , 1998, Neurosurgical focus.

[16]  T. Cascino,et al.  Response criteria for phase II studies of supratentorial malignant glioma. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.