Recent Progress on Tumor Missile Therapy and Tumor Vascular Targeting Therapy as a New Approach

Yasuo      Yoshioka; Yasuo      Tsutsumi; Shinsaku      Nakagawa; Tadanori      Mayumi

Abstract

Tumor targeting therapy, that is “Missile therapy”, using a complex composed of a tumor suppressive drug and a whole antibody against tumor cells, is expected to become an attractive chemotherapy strategy. However, clinically convincing results have not yet been obtained mainly due to poor transport from the circulation to tumor tissue and marked toxicity. Recently, recombinant immunotoxins, composed of an Fv fragment of an antibody to a tumor-related antigen fused to various truncated toxins have been developed to overcome the distribution of immunotoxins in tumors. These recombinant immunotoxins have shown encouraging clinical results for some hematopoietic malignancies. However, there were no significant anti-tumor responses to many tumors, especially solid tumors, probably due to their rapid clearance from the circulation and their immunogenicity and antigenicity. More recently, PEGylation of recombinant immunotoxins has been attempted to overcome these drawbacks. It was found that PEGylation of recombinant immunotoxins improves their effectiveness. We discuss the recent progress in tumor missile therapy. In contrast to others, we developed “Missile therapy against tumor blood vessels” by using specific monoclonal antibodies against tumor endothelial cells rather than actual tumor cells. The complex between antibodies to tumor vascular endothelial cells and anti-tumor drugs can freely access the target cells without concern for their vascular permeability. These preparations have exhibited excellent anti-tumor effects for solid tumors. In this review, we also discuss this vascular targeting therapy as an attractive new strategy for tumor chemotherapy.

Keywords: immunotoxin, pegylation, tumor vascular targeting, antibody, immunoconjugate, tumor necrosis factor-alpha, interleukin-6, tumor endothelial cells