Preface
CpG oligonucleotides as immunotherapeutic adjuvants:innovative applications and delivery strategies ☆
Cytosine –phosphorothioate –guanine oligodeoxynucleotides (CpG ODN)have shown signi ficant potential for treatment of a wide variety of dias including cancer.CpG ODN can be ud either as a stand-alone molecule or as an adjuvant to other therapies.CpG ODN with quence patterns like tho found in bacterial DNA activate potent cell-mediated immune respons [1,2].The speci fic quence motif prent in bacterial DNA that is responsible for triggering the immune respons is the unmethylated CpG dinucleotide flanked by two 5′purines and two 3′pyrimidines [1–4].CpG ODN are taken up by cells via adsorptive endocytosis and bind to the toll-like receptor 9(TLR9)prent within the endosomes in the intracellular compart-ment of B cells and plasmacytoid dendritic cells [5–7].The binding triggers an immunostimulatory cascade inducing the maturation,differentiation and proliferation of multiple immune cells including B and T lymphocytes,macrophages,natural killer cells and monocytes/macrophages that produce interleukin 1,6,12and 18,interferon-γand tumor necrosis factor-α[8–10].
In contrast to anti-n therapeutics which requires continuous and prolonged exposure to the therapeutic nucleotide,the effects of CpG ODN can last for long periods of time even after a brief exposure.On the other hand,the duration,location,and formulation of CpG ODN therapy can have a profound effect on the immune respon,and on the resulting therapeutic effects.This variability in immu-nologic and therapeutic respon is not surprising given that CpG ODN can enhance antigen prentation,improve cellular killing mediated by T cells or NK cells,increa phagocytosis,increa production of cytokines that have anti-tumor effects or initiate proapoptotic effects on malignant cells that express TLR9.Which of the mechanisms is most important therapeutically depends on many factors including the underlying condition being treated,the state of the immune system,the lection of other agents ud in combination with CpG ODN,the route of administration and the formulation of the therapy.
It is therefore to be expected that the ef ficacy of CpG ODN can be substantially improved using a range of drug delivery systems.This theme issue of Advanced Drug Delivery Reviews is to provide a comprehensive summary of the therapeutic potential of CpG ODN in a range of dias and cancer models and the drug delivery systems that are being developed to further enhance CpG ODN adjuvant ef ficacy.Vollmer and Krieg provide a strong current overview of CpG ODN as a TLR9agonist and its therapeutic potential [1,11–13].
Krishnamachari and Salem discuss veral drug delivery strategies for ensuring that both CpG ODN and antigen are co-delivered to the same antigen-prenting cells.The approaches include the u of biodegradable microparticles [14],CpG-antigen conjugates [15],liposomes [16],metallic nanorods [17],pulsatile releasing chips [18],and cell-microparticle hybrids [19].Malyala,O'Hagan and Singh provide a more in-depth review of the u of biodegradable microparticles for delivering CpG ODN whilst Tam offers an analysis of the u of liposomes for enhancing CpG ODN adjuvant ef ficacy in a variety of infectious dias [20–22].Mutwiri and colleagues discuss the u of polyphosphazenes,depot-forming formulations and simultaneous activation with other TLR agonists as methods through which CpG ODNs ef ficacy as an adjuvant can be improved [23].Wagner's review provides an in-depth analysis of CpG ODN-antigen conjugates and their comparison to biodegradable micro-particles [24].The theme issue then covers some of the recent developments on the therapeutic application of CpG ODN.Klinman and colleagues discuss the u of CpG ODN as an adjuvant for treatment of infectious dias [21,25].Fonca and Kline provide an overview of the u of CpG ODN in treating asthma,including its u in preventing development of airway remodelling and inhibition of atopic respons [26,27].Weiner provides an overview of the u of CpG ODN-bad therapy of lymphoid malignancies [28].Lubaroff and Karan discuss the development of CpG ODN as an adjuvant to a vaccine for treating prostate cancer that is bad on a
n adenovirus transduced to express a prostate speci fic antigen [29].Finally Miles and Sandler discuss the u of CpG ODN for treating neuroblastoma either as a standalone molecule or as an adjuvant to alternative vaccine strategies [30].
mcpdThis theme issue on the applications and delivery strategies of CpG ODN brings together a diver and highly inter-disciplinary t of investigators that range from clinicians to basic scientists.The clinical application of CpG ODN as therapeutic agents is just beginning.This issue provides an up to date comprehensive reference guide of the therapeutic potential and complexities of CpG ODN as an immunotherapeutic adjuvant and the advanced drug delivery methods that can be ud to enhance its ef ficacy.
Aliasger K.Salem (Theme Editor)
Division of Pharmaceutics,College of Pharmacy,University of Iowa
Iowa City,Iowa,52242
USA
Corresponding author.
E-mail address:aliasger-salem@uiowa.edu
Advanced Drug Delivery Reviews 61(2009)193–
laborious
194
☆This preface is part of the Advanced Drug Delivery Reviews theme issue on “CpG Oligonucleotides as Immunotherapeutic Adjuvants:Innovative Applications and Delivery Strategies ”
.
Contents lists available at ScienceDirect
Advanced Drug Delivery Reviews
j o u r n a l h o me p a g e :w w w.e l s e v i e r.c om /l o c a t e /a d dr
0169-409X/$–e front matter ©2009Elvier B.V.All rights rerved.doi:10.1016/j.addr.2008.12.003
George J.Weiner
(Theme Editor) Holden Comprehensive Cancer Center at the University of Iowa
Department of Internal Medicine,5970Z JPP,University of Iowa
Iowa City,IA52242
USA
E-mail address:george-weiner@uiowa.edu
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194Preface61(2009)193–194
