GENE-TRANSFER OF CD40-LIGAND INDUCES AUTOLOGOUS IMMUNE RECOGNITION OFCHRONIC LYMPHOCYTIC-LEUKEMIA B-CELLS

CD40-CD40-ligand (CD154) interactions play a critical role in immune a ctivation, Using replication defective adenovirus encoding mouse CD154 (Ad-CD154), we modified human chronic lymphocytic leukemia B cells to express a functional ligand for CD40. This not only induces expressio n of immune accessory molecules on the infected cell, but also allows it to trans-activate noninfected bystander leukemia B cells, Also, fac tors that impair the antigen-presenting capacity of leukemia B cells a re downmodulated. Ad-CD154-infected leukemia cells are highly effectiv e stimulators in mixed lymphocyte reactions and can induce generation of cytotoxic T lymphocytes specific for autologous nonmodified leukemi a cells, As such, Ad-CD154 can induce a host antileukemia response tha t may have therapeutic potential.