Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
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Volume 28, Issue 5
Antibody Delivery - From bench to bedside -
Displaying 1-5 of 5 articles from this issue
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Feature articles "Antibody Delivery From bench to bedside" Editor: Yasuhiro Matsumura
  • Cancer Stromal Targeting
    Masahiro Yasunaga, Shino Manabe, Yasuhiro Matsumura
    2013 Volume 28 Issue 5 Pages 396-405
    Published: November 25, 2013
    Released on J-STAGE: March 01, 2014
    DOIhttps://doi.org/10.2745/dds.28.396
    JOURNAL FREE ACCESS
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    Antibody-drug conjugate (ADC) targeting tumor cells themselves was effective for hematological malignancy or breast cancer having hyper- vascularity and poor stroma. However, it was not effective for the refractory tumors such as brain tumor, scirrhous gastric cancer or pancreatic cancer. Dense stroma prevents the ADC form reaching the tumor cells within the tumor tissues. To overcome "stromal barrier", we created "CAST (Cancer stromal targeting) therapy" using ADC targeting to a tumor stroma. We have succeeded in developing anti-cancer agent (SN-38) conjugated anti-collagen 4 antibody or anti-fibrin antibody. The therapy damaged both tumor cells and tumor vasculature. Bone marrow toxicity, hepatorenal disorder or autonomatous harmful immune response was not recognized. Further evaluation of the CAST therapy is necessary for a future clinical application.
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  • Linker Technology in Antibody-Drug Conjugates for Cancer Treatment
    Shino Manabe
    2013 Volume 28 Issue 5 Pages 406-411
    Published: November 25, 2013
    Released on J-STAGE: March 01, 2014
    DOIhttps://doi.org/10.2745/dds.28.406
    JOURNAL FREE ACCESS
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    Linker technology is important for antibody-drug conjugate development. Linker connects antibody and anti-cancer agent. The linkage between antibody-drug conjugate must be stable during blood circulation, yet the anti-cancer agent should be released at cancer lesion. In this manuscript, the aspect of various linkers and spacers will be described.
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  • Dissection of antibody-antigen interactions for development of antibodies
    Kouhei Tsumoto
    2013 Volume 28 Issue 5 Pages 412-423
    Published: November 25, 2013
    Released on J-STAGE: March 01, 2014
    DOIhttps://doi.org/10.2745/dds.28.412
    JOURNAL FREE ACCESS
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    Antibodies have been widely used for therapeutics and diagnosis due to their high specificity and affinity for the targets; development of antibodies has been extensively investigated in various fields. Once we obtain the genes encoding a monoclonal antibody, we can engineer various molecules using the antibody genes as a recognition element. However, it is not so far since we could understand how an antibody creates the specificity and affinity for the target from structural and energetic viewpoints. In this review, we firstly summarize three methods for biophysical characterization of antibody-antigen interactions. Second, we review our recent progresses on understanding how an antibody recognizes the target antigen from structural and energetic viewpoints. Finally, we discuss how we can create and improve the affinity of an antibody toward the target.
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  • Recent development of antibody drug conjugate
    Kaori Fujimoto-Ouchi
    2013 Volume 28 Issue 5 Pages 424-429
    Published: November 25, 2013
    Released on J-STAGE: March 01, 2014
    DOIhttps://doi.org/10.2745/dds.28.424
    JOURNAL FREE ACCESS
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    An antibody-drug conjugate (ADC) is a new way of formulating antibody drugs that achieves specific binding to the antigen and can deliver the drug to the disease site. The recent advances in antibody specificity, linker technology, and drug optimization have made it possible for ADCs to enter clinical trials. In the present review, I would like to make a summary of ADCs that have been launched or are currently being developed.
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  • Drug delivery into the tumor vasculature with the cell-internalizing monoclonal antibody
    Yohei Mukai , Shinsaku Nakagawa
    2013 Volume 28 Issue 5 Pages 430-438
    Published: November 25, 2013
    Released on J-STAGE: March 01, 2014
    DOIhttps://doi.org/10.2745/dds.28.430
    JOURNAL FREE ACCESS
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    Monoclonal antibodies (mAbs) that are internalized into cells are a current focus in the development of DDS-based drugs such as antibody-drug conjugates (ADCs). The discovery of potent cell-internalizing mAbs, however, requires labor-intensive screening of a massive number of candidates. Here we describe a phage display-based high-throughput screening system to rapidly isolate cell-internalizing mAbs, then also discuss about the efficacy of tumor vascular targeting with cell-internalizing mAbs which target tumor endothelial cells.
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