Cytokine Manipulation of the Immune Response in the Treatment of Human Acute Leukaemia

David      Gottlieb

Abstract

Myeloid leukaemia cells are sensitive to attack by elements of the immune system as evidenced by the effects of T cell depletion, graft versus leukaemia and donor lymphocyte infusion on leukaemic recurrence. An implication is that the immune system can be manipulated to enhance anti-leukaemic effects by exogenous stimulation including the use of immunostimulatory cytokines. These could potentially be used in a controlled manner that avoids the clinical problems associated with graft-versus-host disease. The cytokine used most extensively to date is interleukin-2 (IL2), a molecule that induces T lymphocyte proliferation and the generation of MHC unrestricted cytotoxicity. Despite over 10 years of clinical experience, the data on efficacy in acute myeloid leukaemia remains unclear due to lack of adequate randomised trials. IL2 appears to be effective in patients with low level marrow infiltration by acute myeloid leukaemia (AML) blast cells. It is less effective when patients present or relapse with packed bone marrows. The logical assumption that IL2 treatment given during states of minimal residual disease will reduce the incidence or speed of disease recurrence remains to be adequately tested. IL2 administration is associated with characteristic clinical adverse effects and with specific immuno-haematological changes. The use of other cytokines for immune manipulation in patients with AML is so far essentially limited to the research laboratory. Potential uses include cytokine induced blast differentiation to dendritic cells and the use of irradiated cytokine gene transduced leukaemic cells as vaccines.

Keywords: human acute leukaemia, cytotoxicity

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