Immunotherapeutic applications of CpG-containing oligodeoxynucleotides.
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs stimulate the mammalian immune system to mount a rapid innate immune response. This response is characterized by the production of polyreactive IgM, immunomodulatory cytokines and chemokines. CpG ODN directly stimulate lymphocytes, natural killer cells and professional antigen-presenting cells (such as macrophages and dendritic cells). Owing to the strength and nature of this stimulation, CpG ODN are being harnessed for a variety of therapeutic uses. They are being tested for their ability to act as immune adjuvants, boosting the immune response elicited by conventional and DNA vaccines. As a result of their ability to activate a strong interferon gamma-dominated Th1 response while blocking the development of Th2-dependent allergies, CpG ODN are being examined for their antiallergic properties. Finally, CpG ODN are being used as "immunoprotective agents", since the innate immune response they elicit can protect the host from a variety of pathogenic bacteria, viruses and parasites.
Klinman
D M
DM
Section of Retroviral Research, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Ishii
K J
KJ
Gursel
M
M
Gursel
I
I
Takeshita
S
S
Takeshita
F
F