Basic study on targeted sonodynamic therapy of cancer using photosensitizers and antibodies against tumor antigens.

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To improve the efficacy of the photodynamic therapy of cancer, we tried to develop a new targeted sonodynamic therapy using ultrasound and anti-tumor antibody-conjugated photosensitizers. For this, we first prepared immunoconjugates consisting of the photosensitizer ATX-70 and anti-carcinoembryonic antigen (CEA) mouse monoclonal antibody (mAb), using EDC and sulfo-NHS. This conjugate (F39/ATX-70) showed CEA-specific enhancing effects on the cytotoxicity induced by ultrasound irradiation against tumor cells in vitro. Furthermore, the growth of tumor cells in nude mice was greatly inhibited by ultrasound irradiation when F39/ATX-70 was i.v. injected.Next we tried to use human mAb, instead of mouse mAb, to reduce possible side effects when applied to patients. KM mice, which have the human immunoglobulin genes, were immunized with recombinant MK-1 (Ep-CAM) protein prepared in silkworms, and their spleen cells were fused with mouse myeloma cells. After selection and cloning, several hybridoma clones were obtained that secrete human IgM mAbs against MK-1. We are currently preparing IgG-class HmAbs using different immunization methods. We also obtained a new, improved photosensitizer, DCPH, and are trying to establish a suitable method to conjugate it to mAbs.