モノクローナル抗体結合リポソームによる悪性脳腫ようのターゲティング療法へのアプローチ

Abstract

Malignant glioma is one of the most lethal tumors arising in the central nervous system. The patients with malignant glioma have poor prognosis with an average survival of less than 2 years even if they receive multimodality treatment including surgery and post operative adjuvant therapy. Therefore, we need to develop a new form of therapy that can inhibit the growth and invasion of glioma cells. Here, we have evaluated the efficacy of liposomes conjugated or associated with a monoclonal antibody for malignant glioma. We prepared two types of monoclonal antibodies for the targeting therapy. One is a G-22 monoclonal antibody reactive with the CD44 that overexpresses on the surface of human glioma cells and another is a 3C10 monoclonal antibody reactive with the fusion junction of a deletion-mutant epidermal growth factor receptor (EGFR) on their cells. The deletion-mutant (Type III) was reported to be most prevalent, being approximately 17% of the patients with malignant glioma. Using these antibodies, we prepared the liposomes conjugated or associated with a monoclonal antibody (Immunoliposomes). We were successful with in vitro and in vivo transfer of anticancer drugs or biological response modifiers (BRM) or genes using the immunoliposomes. The immunoliposomes containing methotrexate, cisplatin or adriamycin have selective cytotoxicity toward glioma cells. Also, the immunoliposomes entrapping the BRM genes (ex. interferon-β, tumor necrosis factor-α) increased the growth inhibition of glioma cells much more than the liposomes with no antibody. These results suggest that liposomes conjugated or associated with a monoclonal antibody would be a useful clue for the tumor targeting of malignant gliomas.