Cytotoxic lymphocytes: redirecting the cell-mediated immune response for the therapy of cancer

Cytotoxic CD8+ T cells and NK cells are involved in the elimination of some viruses, graft rejection, antitumour responses, immunoregulation and some autoimmune diseases. The key role of these cells in each of these immune responses and the therapeutic potential they offer when effectively harnessed, has warranted continued interest in their function. A molecular approach has dominated the recent study of cytotoxic lymphocyte function, allowing the characterization of recognition structures on cytotoxic lymphocytes, the definition of two distinct mechanisms of cytotoxicity and the elucidation of their relevance in vivo. Currently, biological and genetic experimental approaches which exploit the targeted cytolytic activity of lymphocytes are being developed for cancer therapy. A greater understanding of the biology of cytotoxic lymphocytes when adoptively transferred, the development of re-engineered mAbs with tailored properties and the characterization of newly defined endogenous tumour cell antigens, has brought us to the brink of using these cells to greater therapeutic advantage. This review briefly examines ongoing efforts to characterize the mechanism of action of cytotoxic lymphocytes and describes the progression of approaches designed to enhance the anti-tumour activity of these cells.