Antibody-mediated molecular-targeted therapy for adult T-cell leukemia: recent progress and future challenges in the treatment of cancers

Abstract

The role of the secreted matricellular molecule osteopontin (OPN) and its receptor integrins in the pathogenesis of adult T-cell leukemia (ATL) and the possible applications of an anti-OPN monoclonal antibody (mAb) for ATL immunotherapy in NOD/Shi- scid , IL-2R g null (NOG) mice were investigated. Subcutaneous inoculation of ATL cell lines into NOG mice led to increased plasma levels of OPN, correlating well with metastasis of the inoculated cells and survival time. This result suggested that the xenograft NOG mouse model could be a useful system for in vivo assessment of the physiological role of OPN in ATL pathogenesis. Intraperitoneal administration of an anti-OPN mAb resulted in the inhibition of tumor growth, tumor invasion, and metastasis. In addition, the mAb treatment led to reduction in the number of fibroblasts expressing fibroblast activation protein. We have shown here a novel mAb-mediated therapeutic strategy targeting the interaction between OPN from stromal cells and integrins on the tumors of ATL patients. In this editorial research highlight, we also comment on the recent progress in the development of mAbs and their advanced counterparts, the antibody-drug conjugate, for the treatment of cancers.