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The number of clinical trials investigating the use of nucleic acid drugs, including DNA/RNA-based vaccines, immunostimulatory/modulatory DNA/RNA and cyclic dinucleotides, for immuno-prophylaxis and -therapy has been increasing exponentially in recent years. These new drugs have revealed their therapeutic potential not only as vaccines or adjuvant therapies, but also as monotherapies for use in immuno-therapy of cancer and allergic disease. I will present an overview of their current R&D taking place in this field, then describe our recent progress, particularly regarding CpG oligodeoxynucleotides (ODNs), such as K3, K3-SPG, and D35 as either vaccine adjuvants or mono-immunotherapeutic agents for tropical diseases including malaria and leishmaniasis.

A 53-year-old man was admitted to our hospital with the complaint of neck pain and dyspnea. His blood examination revealed increased C-reactive protein and amylase levels. Enhanced computed tomography (CT) images demonstrated a retropharyngeal and a mediastinal low-density area extending to the portal area. He was diagnosed with pancreatic pseudocyst from the abdominal cavity to the cervical region accompanied by spontaneous rupture into the portal vein. Endoscopic ultrasound-guided cyst drainage (EUS-CD) of the most inferior cavity around the superior mesenteric artery was performed through the gastric wall. No adverse events were recorded during the procedure, and a near-complete resolution of his symptoms and the pseudocyst was achieved.

Recent progress in immunology have revealed that the immune system is capable of fight- ing against cancer by not only activation of innate and adaptive immune responses, but also by inhibition of various types of the cancer-associated immune suppression. In addition to immune check-point inhibitors and cancer vaccines, many conventional and new generations of vaccine adjuvants are in the limelight, many of which are known as potent immuno- stimulators through specific innate immune receptors and signaling pathways. For example, TLR agonist targeting the tumor microenvironment, or combination of certain TLR agonist with STING ligand can act not only as a potent adjuvant for various modality of cancer vac- cines, but also as a mono-therapeutic agent for various cancer animal models. Their precise mechanisms of action have not been fully elucidated, but evidence suggest that adjuvants mentioned above reverse an immune suppressive tumor microenvironment into an optimal vaccination spot by providing protective tumor (neo) antigens and immunogenic cell death.

Particulates are considered to be one of the causative factors for allergic asthma and rhinitis in developed countries. Indeed, particulates and crystals are reported to activate type-2 immunity, which is associated with allergic responses. Thus far, many studies have been carried out to determine how particulates trigger immune responses; however, the detailed mechanisms by which immune responses are triggered are still unknown. One important clue is that particulates have an adjuvant activity and boost immune responses toward type-2 responses. Most adjuvants are considered to activate innate immunity, and then activated innate immune cells stimulate adaptive immunity, which involves T cells and B cells. That is why many scientists believe that particulate adjuvants directly stimulate innate cells through unique sensor proteins such as pattern-recognition receptors. In this review, we will introduce the proposed mechanisms of particulate-induced immune activation from the viewpoint of the activation of innate immune responses and related receptors and sensors.

Since the discovery of the human T cell-defined tumor antigen, the cancer immunotherapy field has rapidly progressed, with the research and development of cancer immunotherapy, including cancer vaccines, being conducted actively. However, the disadvantages of most cancer vaccines include relatively weak immunogenicity and immune escape or exhaustion. Adjuvants with innate immunostimulatory activities have been used to overcome these issues, and these agents have been shown to enhance the immunogenicity of cancer vaccines and to act as mono-therapeutic anti-tumor agents. CpG ODN, an agonist for TLR9, is one of the promising nucleic acid-based adjuvants, and it is a potent inducer of innate immune effector functions. CpG ODN suppresses tumor growth in the absence of tumor antigens and peptide administration. Therefore, CpG ODN is expected to be useful as a cancer vaccine adjuvant as well as a cancer immunotherapy agent. In this review, we discuss the potential therapeutic applications and mechanisms of CpG ODN for cancer immunotherapy.

The SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Previous clinical trials indicated the protective efficacy of BK-SE36 malaria vaccine that is constituted of SE36 recombinant protein and aluminum hydroxide gel. In this study, we assessed the safety, immunogenicity and protective efficacy of SE36/AHG formulated with TLR9 ligand adjuvants K3 CpG oligodeoxyribonucleotides (CpG ODNs) (K3 ODN), D3 ODN or synthetic hemozoin, in two non-human primate models. SE36/AHG with or without each adjuvant was administrated to cynomolgus monkeys. A combination of TLR9 ligand adjuvant with SE36/AHG induced higher humoral and cellular immune response compared with SE36/AHG alone. The most effective TLR9 ligand, K3 ODN, was chosen for further vaccine trials in squirrel monkeys, in combination with SE36/AHG. All monkeys immunized SE36/AHG with K3 ODN effectively suppressed parasitemia and symptoms of malaria following challenge infection. Furthermore, no serious adverse events were observed. Our results show that the novel vaccine formulation of K3 ODN with SE36/AHG is safety, potent immunogenicity and efficacy in nonhuman primates. We are conducting the first in human clinical trials with this formulation.

Inducing adaptive immune responses with vaccination requires prior innate immune responses. Adjuvants have been used empirically to enhance and modulate the adaptive immune responses elicited by the vaccination. Advances in the innate immune system revealed that many adjuvants act through the innate immune receptors including TLRs, NLRs, RLRs, and CLRs. Recently it has been shown that some particulate adjuvants directly activate dendritic cells in a receptor-independent manner. In this review, we discuss how adjuvants activate dendritic cells, directing adaptive immune responses to Th1, Th2, and Th17 cells. We also discuss a differential requirement of adjvuant between priming and boosting administration of vaccine, and appropriate use of adjuvants to reduce the side effect of vaccine.

Intramedullary spinal cord cavernous hemangiomas (angiomas) are occult vascular malformations characterized by rare lesions consisting of closely packed capillary-like vessels. In general, patients with this disease become symptomatic because of hemorrhage leads to progressive neurological deficits. Therefore, surgical tumor resection should be considered for symptomatic patients should be considered a surgical tumor resection.

A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.