Cytotoxic lymphocyte-mediated immunotherapy.
Cytotoxic CD8+ T cells and NK cells play a role in the elimination of some viruses, graft rejection, antitumour responses, immunoregulation and some autoimmune diseases. The central importance of these cells in each of these immune responses and the therapeutic potential they offer, when effectively targeted, has justified continued interest in their function. Molecular biology has dominated the recent study of cytotoxic lymphocyte function, allowing the characterisation of recognition structures on cytotoxic lymphocytes, the definition of two distinct mechanisms of cytotoxicity and the determination of their relevance in vivo. Biological and genetic experimental approaches which exploit the targeted cytolytic activity of lymphocytes are now being developed for immunotherapy. A greater knowledge of the biology of cytotoxic lymphocytes when adoptively transferred, the development of engineered monoclonal antibodies and the characterisation of novel endogenous tumour cell antigens, has us on the brink of using these cells to greater therapeutic advantage. This article reviews ongoing efforts to characterise the mechanism of action of cytotoxic lymphocytes and outlines the progression of approaches designed to enhance the anti-tumour activity of these cells.
Smyth
M J
MJ
Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin Hospital, Melbourne, Vic.
Kershaw
M H
MH
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm