title: A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2.
abstract: Most B-cell malignancies are incurable diseases and therefore warrant new therapeutic approaches. In a pilot study, we tested the feasibility and safety of combined immunotherapy consisting of adoptive transfer of autologous tumour-specific T cells, low-dose interleukin 2 (IL-2) and a cellular vaccine of CD40-activated plasma cell leukaemia (PCL) cells in a patient who failed tandem repeat stem cell transplantation and idiotype vaccination. Autologous tumour-specific T cells for adoptive T-cell transfer were propagated in vitro by repetitive stimulation with autologous ex vivo CD40-activated PCL cells. CD40-activated PCL cells for vaccination were similarly generated ex vivo by co-culture with CD40 ligand transfectants. Autologous T cells (5 x 108 and 2.5 x 109 for two separate treatment cycles) generated ex vivo and cytotoxic against autologous tumours were infused and well tolerated by the patient. Fever and myalgias were closely related to IL-2 injections and no other adverse effects were observed. A temporary decrease of PCL cells 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) demonstrated loss of MHC class II, and (3) did not induce autologous tumour-specific 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 tumour cells, either as a vaccine or for ex vivo stimulation of autologous T cells.
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. schultze@mbcrr.harvard.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Schultze
authors.forename: K C
authors.initials: KC
authors.lastname: Anderson
authors.forename: M H
authors.initials: MH
authors.lastname: Gilleece
authors.forename: J G
authors.initials: JG
authors.lastname: Gribben
authors.forename: L M
authors.initials: LM
authors.lastname: Nadler
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D019013:CD40 Antigens; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007952:Leukemia, Plasma Cell / Q000628:therapy*; D008213:Lymphocyte Activation; D008875:Middle Aged; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000637:transplantation*; D016896:Treatment Outcome
chemical_list: D019013:CD40 Antigens; D007376:Interleukin-2