Enhancement of cALL immunogenicity by co-culture with a CD154 expressing 293 cell line

Pre-B cell acute lymphoblastic leukaemia (cALL) commonly occurs in young pa tients and although successful conventional therapies are available (such a s cytotoxic drugs and bone marrow transplantation) for a proportion of pati ents (approximately 30%) these are ultimately unsuccessful. Recurrence of d isease is a result of the failure of the immune system to recognize these a bnormal cells and down-regulation of crucial molecules required for cognate CD4(+) T cell recognition has been postulated as a means of immune escape. In this study we show that an embryonic kidney cell line (293 cells) trans fected with CD154 (40 L.1) are capable of not only maintaining the viabilit y of primary ALL cells in culture but can also up-regulate the expression o f a number of crucial molecules involved in antigen recognition. We show th at 40 L.1 cell stimulation of primary ALL cell cultures can not only enhanc e the allogeneic and autologous MLR response to such cells but will also in duce CTL effectors which are capable of lysing wild-type autologous ALL cel ls. It is therefore conceivable that such an approach could be used to gene rate an active anti-tumour response in patients, following conventional the rapy, reducing the incidence of recurrence.