Enhanced retroviral gene transfer into CML and normal bone marrow, and CMLand mobilized peripheral blood CD34(+) cells using the recombinant fibronectin fragment CH-296

Autologous stem cell transplantation is a therapeutic alternative for many chronic myeloid leukaemia (CML) patients ineligible for the only curative t reatment of allogeneic bone marrow transplantation In this study the retrov iral transduction of CD34(+) progenitor cells isolated from the bone marrow (BM) and peripheral blood (PB) of patients with CML was compared to that o f CD34(+) cells isolated from the BM and PB of normal individuals and patie nts with non-haematological malignancies. A highly significant increase in transduction of all cell types was achieved in the presence of the recombin ant fibronectin fragment, CH-296 (P < 0.05). In the absence of fibronectin, centrifugation produced a marginal improvement in the transduction of all cell types, which was significant only for CMLBM progenitor cells (P < 0.05 ). There was no significant additive effect when centrifugation was include d in the fibronectin infection protocol. In the presence of CH-296, combina tions of three or more cytokines improved transduction for all cell types. The same degree of transduction was observed for both normal and CML cells, irrespective of the variations employed in the infection protocol, suggest ing that both leukaemic and non-leukaemic progenitors are equally susceptib le to retroviral infection. These results demonstrate that CH-296 has a uni versal beneficial effect on the transduction of haemopoietic progenitor cel ls, with clear potential for future clinical trials.