A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2

Most B-cell malignancies are incurable diseases and therefore warrant new t herapeutic approaches. In a pilot study, we tested the feasibility and safe ty of combined immunotherapy consisting of adoptive transfer of autologous tumour-specific T cells, low-dose interleukin 2 (IL-2) and a cellular vacci ne of CD40-activated plasma cell leukaemia (PCL) cells in a patient who fai led tandem repeat stem cell transplantation and idiotype vaccination. Autol ogous tumour-specific T cells for adoptive T-cell transfer were propagated in vitro by repetitive stimulation with autologous ex vivo CD40-activated P CL cells. CD40-activated PCL cells for vaccination were similarly generated ex vivo by co-culture with CD40 ligand transfectants. Autologous T cells ( 5 x 10(8) and 2.5 x 10(9) for two separate treatment cycles) generated ex v ivo and cytotoxic against autologous tumours were infused and well tolerate d by the patient. Fever and myalgias were closely related to IL-2 injection s and no other adverse effects were observed. A temporary decrease of PCL c ells in peripheral blood was seen after the first cycle of adoptive T-cell therapy, tumour cell vaccination and low-dose IL-2. Tumour progression was associated with tumour cells that (1) expressed a complex karyotype, (2) de monstrated loss of MHC class II, and (3) did not induce autologous tumour-s pecific T-cell lines ex vivo. We demonstrated the safety and feasibility in combining autologous tumour-specific T-cell therapy with low-dose IL-2 and that clinical trials based on the use of CD40-activated autologous tumour cell vaccines are warranted in patients with CD40-activated autologous tumo ur cells, either as a vaccine or for ex vivo stimulation of autologous T ce lls.