Immune and cell therapy of hematologic malignancies

Advances in molecular biology and immunology have identified means to activate the immune response against leukemia-associated antigens. Recent studies indicate that the stealth-like phenotype of leukemia cells can be reversed through transfer of genes encoding recombinant membrane-stabilized proteins of the tumor necrosis factor (TNF) imily, such as the one encoding CD154, the ligand for CD40. A phase I clinical trial using autologous CD154-transduced leukemia cells as a cellular vaccine has provided encouraging results. Treatment not only appears capable of inducing a cellular anti-leukemia immunity, but also may have a direct effect on leukemia cells by inducing latent sensitivity to Fas (CD95)-dependent leukemia-cell apoptosis. Phase II studies currently are underway using multiple injections of autologous leukemia cells made to express recombinant CD154 via gene transfer. Conceivably, we may be entering an era of effective gene therapy for hematologic malignancies.