Harnessing T-lymphocytes for human cancer immunotherapy

Abstract

After nearly a decade of controversy, the concept of adoptive immunotherapy in humans is gaining greater acceptance. More recently, investigators have made use immunotherapeutically of T-lymphocytes nonspecifically activated in vitro by a number of agents, including lymphokines, lectins, and autologous and allogeneic tumor cells. The limitations for the investigational use of these highly specialized and "educated" lymphocytes have been the inability to generate sufficient numbers of cells in vitro for adoptive transfer experiments and to sustain their growth over long periods of time. While marked success has been demonstrated over the years in tumor-bearing animal models, the feasibility of such work in humans has been greatly improved by the experimental expansion and maintenance of immune lymphocytes (those exposed to antigenic challenge) in vitro using either highly purified or recombinant, interleukin 2. As a result, large numbers of lymphocytes can successfully be infused into patients, and whole body scans can show migration of these labeled cells to the lung, liver, and spleen. The use of nontoxic, nonspecific activated "killer" lymphocytes is an innovative approach with enormous potential. This report presents discussion of these findings and addresses the issue of an alternative approach to cancer treatment therapy, the in vivo use of cloned cytotoxic T-lymphocytes sensitized to the autologous tumor.