Intravital fluorescent imaging is a cutting-edge, powerful tool for identifying novel therapeutic targets as well as studying ‘real’ modes of action of various molecule-targeted drugs in vivo tissue/cellular levels. By using an original multiphoton microscopy in our hand, we have been studying on ‘real’ cellular dynamics with immune and inflammatory systems in intact tissues and organs, both in physiological and pathological conditions. Especially we have first succeeded in visualizing in vivo behaviors of different cell types in bones, such as osteoclasts, which led to significant conceptual advances on dynamic bone/immune systems. This research activity with dynamic imaging technology is not only contributing to development of basic biological science in general, but also serving as a novel way for analyzing in vivo pharmacological actions of different emerging drugs, biotechnology-based medicine chief among them, such as monoclonal antibodies and tumor-killing bioengineered lymphocytes. In this project, we utilize advanced intravital imaging technology for developing the novel system for analyzing in vivo modes of actions of different biological drugs to facilitate further drug discovery.
For example, we plan to newly establish the intravital imaging systems for drug screening, such as skin inflammation, allergic reaction in airway, and neuroinflammation in spinal cord. In addition, we will develop the system for evaluating the activity of CAR-T cells against leukemic cells in bone marrow. Furthermore, we also plan to develop novel image-analysis software for automatic quantification and statistical analyses, which would be necessary for quantitatively and reproducibly evaluating pharmacological actions of different new drugs in vivo.
Figure 1: Laboratory for intravital imaging analyses
Figure 2: In vivo pharmacological analysis and drug discovery for novel bioengineered medicine based on advanced intravital imaging system
Figure 3: An example of in vivo pharmacological analyses based on intravital imaging technology. Bone-protecting effects of different biological agents used for treating rheumatoid arthritis (anti-TNFα mAb, anti-IL-6R mAb, CTLA4-Ig) were evaluated with inflammation-induced bone destruction model. In results, both anti-TNFα mAb and anti-IL-6R mAb, but not CTLA4-Ig, had potency for blocking bone-destroying activity of mature osteoclasts.