Valutazione della fattibilità dell'espansione delle cellule CIK chimeriche in condizioni GMP a partire da pazienti con diagnosi di Leucemia Acuta Mieloide (LAM) sottoposti a trapianto allogenico di Cellule Staminali Ematopoietiche

Acute Myeloid Leukaemia (AML) is a haematological disorder consisting in the expansion of immature myeloid cells that is usually more predominant in the men population and accounts for the 20% of all childhood leukaemia. Given the high incidence of AML relapse after standard treatment combined with a significantly decreased chance of survival, novel therapeutic approaches have been searched. Cytokine Induced Killer (CIK) cells represent one of the most applicable options, thanks to their extensive studies, both in vitro and in vivo. CIK cells can be expanded ex vivo from Peripheral Blood Mononuclear Cells (PBMCs), bone marrow mononuclear cells and umbilical cord blood and raise particular interest in the field of immunotherapy because of their ability to exert an MHC-unrestricted cytotoxic anti-tumour activity against a broad range of tumours. The aim of this study, as part of the pilot study (ID: CIKAML) “Pilot study for the evaluation of the Cytokine-Induced Killer (CIK) cells ex vivo expansion feasibility in compliance with GMP requirements from patients diagnosed with Acute Myeloblastic Leukaemia (AML) and Myelodysplastic Syndrome (MDS) who underwent allogeneic Hematopoietic Stem Cell (HSCs) Transplant”, is to evaluate the feasibility of expansion of CIK cells isolated from AML patients who have previously undergone allogeneic Hematopoietic Stem Cell Transplantation (HSCT), as a prophylactic therapy against post-transplant relapse, following the Good Manufacturing Practice (GMP) guidelines. We enrolled four paediatric patients, according to the inclusion criteria of the protocol, and we expanded CIK cells from peripheral blood. In parallel, 4 healthy donors were used as a control of the previously characterised and GMP validated CIK cell expansion procedure. In the context of ex vivo expansion from different individuals, there is a great inter biological variability and indeed we witnessed several differences in the cell behaviour during the expansion process. Overall, patient expanded CIK cells showed a lower fold increase in respect to the one from healthy donors and a similar pattern was observed in terms of viability, immunophenotype and cytotoxicity. Contrary to what we have seen in pre-clinical studies, CIK cells show a great difficulty in terms of expansion and differentiation from AML patients post-HSCT under GMP conditions. However, these results were affected by the limited number of patients analysed, and the enrolment of further patients is required to perform a statistical analysis and determine the actual feasibility of this approach.