title: An immune edited tumour versus a tumour edited immune system: Prospects for immune therapy of acute myeloid leukaemia.
abstract: Cell based therapies for acute myeloid leukaemia (AML) have made significant progress in the last decade benefiting the prognosis and survival of patients with this aggressive form of leukaemia. Due to advances in haematopoietic stem cell transplantation (HSCT) and particularly the advent of reduced intensity conditioning (RIC), the scope of transplantation has now extended to those patients previously ineligible due to age and health restrictions and has been associated with a decrease in transplant related mortality. The apparent graft versus leukaemia (GvL) effect observed following HSCT demonstrates the potential of the immune system to target and eradicate AML cells. Building on previously published pre-clinical studies by ourselves and others, we are now initiating a Phase I clinical study in which lentiviral vectors are used to genetically modify AML cells to express B7.1 (CD80) and IL-2. By combining allogeneic HSCT with immunisation, using the autologous AML cells expressing B7.1 and IL-2, we hope to stimulate immune eradication of residual AML cells in poor prognosis patients that have achieved donor chimerism. In this report we describe the background to cell therapy based approaches for AML, and discuss difficulties associated with the deployment of a chronically stimulated, hence exhausted/depleted immune system to eradicate tumour cells that have already escaped immune surveillance.
authors.affiliation: King's College London, Department of Haematological Molecular Medicine, The Rayne Institute, 123 Coldharbour Lane, SE5 9NU, London, UK.
authors.forename: Lucas
authors.initials: L
authors.lastname: Chan
authors.forename: Nicola R
authors.initials: NR
authors.lastname: Hardwick
authors.forename: Barbara-ann
authors.initials: BA
authors.lastname: Guinn
authors.forename: Dave
authors.initials: D
authors.lastname: Darling
authors.forename: Joop
authors.initials: J
authors.lastname: Gäken
authors.forename: Joanna
authors.initials: J
authors.lastname: Galea-Lauri
authors.forename: Aloysius Y
authors.initials: AY
authors.lastname: Ho
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Farzin
authors.initials: F
authors.lastname: Farzaneh
mesh_terms: D000208:Acute Disease; D002986:Clinical Trials as Topic; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016086:Lentivirus / Q000235:genetics; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000628:therapy*; D019139:Tumor Escape / Q000276:immunology