Biological treatment in acute myelogenous leukaemia: how should T-cell targeting immunotherapy be combined with intensive chemotherapy?
T-cell targeting immunotherapy is now considered as a possible strategy in the treatment of acute myelogenous leukaemia (AML). Clinical importance of antileukaemic T-cell reactivity after allogeneic stem cell transplantation (SCT) is well established and the early experience from IL-2 therapy suggests that even autologous T-cells can mediate antileukaemic reactivity. The clinical experience also indicates that immunotherapy should begin when the leukaemia cell burden is minimal, and the detection of an operative cellular immune system, even in patients with chemotherapy-induced cytopenia, further suggests that it is possible to begin T-cell targeting therapy early after chemotherapy while patients are still cytopenic. However, adult patients in particular have a T-cell defect after chemotherapy that may last for several months. For this reason immunotherapy should probably be continued or repeated until a maximal effect is achieved when the patients no longer have a T-cell defect. This treatment approach may also be considered in combination with autologous SCT. T-cell targeting regimens should include, if possible, several therapeutic components. Firstly, native AML blasts can function as accessory cells during T-cell activation and in vivo therapy with T-cell growth factors (e.g., IL-2, IL-15) may then enhance antileukaemic reactivity or non-specific cytotoxicity against the AML cells; and secondly, a further enhancement of AML-specific reactivity may be achieved by vaccination with AML-specific peptides, immunisation with AML-blasts expressing a dendritic cell phenotype, or exposure to normal antigen-presenting cells (APC) pulsed with or expressing AML-specific peptide sequences.
Bruserud
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Division of Hematology, Department of Medicine, Haukeland University Hospital and the University of Bergen, Norway. oystein.bruserud@haukeland.no
Wendelboe
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D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D007167:Immunotherapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology