IMPROVING THE EFFICACY OF ANTIBODY-BASED CANCER THERAPIES

  • Phùng Thị Thu Hằng

Abstract

A quarter of a century after their advent, monoclonal antibodies have become the most rapidly expanding class of pharmaceuticals for treating a wide variety of human diseases, including cancer. Although antibodies have yet to achieve the ultimate goal of curing cancer, many innovative approaches stand poised to improve the efficacy of antibody-based therapies. Antibodies have started to fulfil their promise as anticancer therapeutics with the five antibodies now marketed as drugs in the United States (Rituxan,Herceptin, Mylotarg and Alemtuzumab (Campath)) and Germany (Panorex).The current emphasis on antibody therapies for non-solid (for example, lymphomas and leukaemias) over solid tumours probably reflects the much greater accessibility of antibodies to non-solid tumours, resulting in improved antibody localization and enhanced efficacy. For solid tumours, targeting minimal residual and micrometastatic disease is attractive as it obviates the need to penetrate bulky tumours. Unfortunately, this approach might be stymied by the need for very large and costly trials with multiyear follow-up for statistical assessment of treatment outcome. It has proved seductively simple to enhance the antitumour efficacy of many antibodies in xenograft studies. This reflects the fact that antibody localization to tumours in mice is often efficient, aild targeting antibodies bind human antigens but commonly not the corresponding mouse antigens. By contrast, clinical experience with the same antibodies has often been marked by a lack of efficacy and/or significant toxicity that probably reflects the limited accrual at the tumour site(s) and binding to antigen-positive non-tumour tissue, respectively. Such disappointing clinical data might provide insights into ways to create potentially more efficacious and safer anti tumour antibodies. Certainly, the concept of enhancing the antitumour activity of antibodies in cancer patients has been established, but doing so within the realm of manageable toxicities remains an ongoing challenge.

Tác giả

Phùng Thị Thu Hằng
điểm /   đánh giá
Published
2011-11-25
Section
Articles