Masahiro Yasunaga

Microscopic Mass Spectrometry for the Precise Design of Drug Delivery Systems

To bring drugs formulated in drug delivery systems (DDS) successfully into the clinic, preclinical studies have to be conducted which are aimed at obtaining pharmacological data relevant to the clinical application of such drugs. For such preclinical studies high-performance liquid chromatography (HPLC) or liquid chromatography mass spectrometry (LC-MS) is generally used. However, these methods do not generate data about the drug distribution in a specific target area, although obtained data allow optimizing the drug design in order to achieve a more efficient targeted delivery.

A New Chemiluminescent Enzyme Immunoassay for Plasma Tissue FactorDetection

High concentrations of tissue factor (TF) in the plasma may have a major role in the elevated risk of thrombosis in patients with malignant diseases. The quantification of plasma TF concentrations in cancer patients may enable accurate assessments of the risk of thrombosis during the process of cancer progression. Whether the plasma TF concentration is associated with the tumor volume in pancreatic cancer in the field of cancer biology remains uncertain. Rat anti-human TF monoclonal antibodies were prepared in our laboratory and were used in a chemiluminescent enzyme immunoassay (CLEIA) for TF detection. In an in vitro experiment, the antibodies for human TF did not crossreact with mouse TF. Therefore, tumor-derived TF was specifically detected using a novel sensitive human TF detection system developed for this study. The plasma concentration of tumor-derived TF was positively correlated with the tumor volume in mice bearing the human pancreatic cancer cell line BxPC-3. Thus, the plasma TF concentration may be a useful tumor marker. These data warrant further preclinical and clinical investigations of our CLEIA system.

Cancer Stromal Targeting (CAST) Therapy and Tailored Antibody Drug Conjugate Therapy Depending on the Nature of Tumor Stroma

In spite of recent success of monoclonal antibody (mAb) drug conjugate (ADC) therapy in patients with hypervascular and special tumors recognized by a particular mAb, there are several issues to be solved for ADC counted as universal therapy for any types of cancer. Especially most human solid tumors possess abundant stroma that hinders the distribution of ADC. To overcome these drawbacks, we developed a unique strategy that the cancer stromal targeting (CAST) therapy by cytotoxic immunoconjugate bound to the collagen IV or fibrin network in the tumor stroma from which the payload is released gradually and distributed throughout the tumor, resulting in the arrest of tumor growth due to induced damage to tumor cells and tumor vessels.