Gene therapy and active immune therapy of hematologic malignancies.
Gene therapy for patients with hematologic malignancies, particularly chronic lymphocytic leukemia (CLL), have focused on transducing primary leukemia cells with a virus vector to express immune-stimulating genes which can induce and propagate a productive and clinically significant immune response against the malignant cells. A variety of replication-defective vectors has been studied to transduce genes for cytokines and function-associated surface molecules. Active vaccines have been developed in vitro, and their activity has been confirmed in clinical trials. Ongoing work aims to optimize this strategy and to identify the appropriate and optimal patient groups in which to apply vaccine therapy. Clinical trials also have provided insight into unexpected alternative mechanisms through which these strategies might provide a clinical benefit.
Wierda
William G
WG
Department of Leukemia, Division of Cancer Medicine, UT MD Anderson Cancer Center, PO Box 301402, Houston, TX 77230-1402, USA. wwierda@mdanderson.org
Kipps
Thomas J
TJ
D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000627:therapeutic use; D051940:B7-2 Antigen / Q000627:therapeutic use; D023201:CD40 Ligand / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015316:Genetic Therapy; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D016233:Immunotherapy, Active; D018664:Interleukin-12 / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor