Antibodies play a central role in humoral immunity and have been developed not only as reagents for the detection and diagnosis but also as clinical products due to its high affinity and specificity. Approximately 20 therapeutic antibodies have been approved by the FDA, and there are more than 100 additional antibodies in clinical development. In the development of antibody drugs, problems such as limited efficacy and high production costs have become so serious that attempts are now being made to construct highly effective and potent recombinant antibodies from human and/or humanized protein fragments. In this review, we focused on bispecific antibodies retargeting of lymphocytes against tumor cells and introduced its perspective as a novel reagent for cancer therapy.

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Stem cells or progenitors derived from non-neural samples as well as the neural tissues in humans are thought to be a good candidate for the regenerative medicine in central nervous system (CNS) diseases. The characteristics of these stem cells are high proliferating potential and multipotential. They showed good adaptation in the host CNS, migrated through the normal and damaged brain tissue, and differentiated upon the host microenvironment subsequent to transplantation. These characteristics seem to be very useful to establish a cell therapy for CNS diseases.
A distinct advantage of a stem cell therapy using autologous bone marrow for CNS diseases such as stroke is a longer therapeutic time window, whereas the majority of the present treatments for stroke have an interventional time window of only hours. The present project will be able to represent a novel technology for a therapeutic strategy for CNS diseases including stroke. Given the severity and frequency of stroke, such an approach could have a very significant impact on the medical, social and economical consequences.

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In mucosa-associated lymphoid tissues (MALT), such as Peyer's patches and nasopharynx-associated lymphoid tissues, all types of immunocyte including dendritic cells, T cells, B cells and others are present and form the mucosal immune network against invasion of luminal pathogenic bacteria or virus. M cells are known to be antigen-sampling cells located in the follicle-associated epithelium (FAE) of MALT and play an important role as gateway of mucosal epithelial barrier. In this review, we shed light on the recent progress of protein antigen delivery system to MALT with M cell-targeting technology for the creation of new generation of mucosal vaccine.

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In recent years, RNA aptamers have been regarded as the next generation of antibody therapeutic drugs. RNA aptamers are selected by in vitro selection referred to as SELEX and after going through truncation and modification, they become candidates for therapeutic drugs. PEGylation is used for substantial improvement of pharmacokinetics. An aptamer itself is potentially a therapeutic drug, but it can also be used as a drug delivery agent by conjugating it with an agent such as an anti-cancer agent. In this review, developmental processes and typical properties of aptamer therapeutic drugs will be reviewed. vWF aptamer, which is now in phase II clinical studies, and MK aptamer, which is being developed by RIBOMIC Inc., will be also reviewed.

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In order to develop a siRNA drug, chemical modification and formulation of siRNA are required. We prepared long-term sustained release microspheres (msp) encapsulating siRNA with a cationic carrier. The siRNA msp achieved a persistent suppression of tumor growth in S-180 bearing mice.

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Transfusion by blood platelets is established therapy for patients with bleeding phenotypes or diseases. An insufficient supply of platelet concentrate is being caused by the unstable properties of platelets that should keep at room temperature and are useful within only 3-4 days, which is different from case of red blood cells. Embryonic stem cells (ESCs) could potentially compensate for the lack of availability for blood platelets used in transfusions. Recently established induced pluripotent stem (iPS) cells could be an alternative source for generating platelets in vitro replacing of donor blood that may cause various infectious diseases.

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A fundamental obstacle in systemic therapy for metastatic cancer patients is specific targeting of therapy directly to a solid tumor. Hypoxic or necrotic regions are characteristic of solid tumors in many human tumors. A strain of anaerobic bacteria such as Bifidobacterium or Clostridium selectively localizes to and proliferates in solid tumors after systemic application. Another approach uses attenuated Salmonella strains that need tumor-specific nutrients to selectively proliferate and is a potential gene delivery system. We constructed a plasmid, pBLES100-S-eCD, which included the cytosine deaminase gene. Transfected Bifidobacterium longum produced cytosine deaminase in the hypoxic tumor. Enzyme/prodrug therapy was confirmed to be effective for systemic administration.

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