Adoptive cellular immunotherapy

Introduction The possibility that the immune system can be harnessed to play a role in eradicating leukemia has long been an attractive concept. Numerous experiments in animal models have convincingly shown that T lymphocytes recognize and kill malignant cells. However, human immunotherapy with nonspecific stimulants, such as BCG (Calmette–Guérin bacillus), has not had a successful history. In the last few years, improved knowledge of the molecular basis of antigen presentation and T-cell recognition of antigen has made it clear that many tumors possess antigens that could be targets for activated T cells. Interest in cellular immunotherapy has also been stimulated by clinical studies showing the efficacy of unmanipulated donor T cells as therapy for relapse after allogeneic bone marrow transplantation. In this chapter we review clinical immunotherapy strategies now being applied in the treatment of leukemia. Immune system recognition of tumor cells Recent advances in basic immunology have provided important insights into the mechanisms by which the immune system recognizes tumor cells. Dissection of the processes of antigen presentation and T-cell recognition of antigen has yielded especially useful information in this regard. Advances in genomics have also simplified the identification of putative tumor antigens through the use of new informatics tools to deduce epitopes from candidate genes. Antigen presentation Antigen-presenting cells recognize either endogenous cellular proteins or exogenous proteins, such as tumor debris, process them into short peptide fragments, and then present these fragments on the cell surface in association with MHC molecules for subsequent presentation to T cells.