Current Gene Therapy - Volume 2, Issue 1, 2002

One of the main barriers to more efficacious use of modern chemotherapeutic agents, is the collateral toxicity exhibited in normal, highly proliferative tissues, primarily the haemopoietic, gastrointestinal and Pulmonary tissues. Drug resistance of tumours to these drugs compounds this problem. This review discusses the role of O6-alkylguanine-DNA alkyltransferase (ATase) in conferring protection against O6-alkylating a Read More

Transplantation offers a unique opportunity for gene transfer into allografts before grafting. After organ retrieval, the cold ischemic period renders organs available for manipulation and gene transfer. Local expression of protective or immunomodulatory molecules within the graft environment offers a better local bioavailability of bioreagents and potentially less systemic side effects. Protection against ischemia-reperfusion injur Read More

Lentiviral vectors based on HIV-1, HIV-2, or SIV have the ability to transduce dividing and non-dividing T cells, dendritic cells, hematopoietic stem cells and macrophages, which are the main target cells for gene therapy of HIV-1 infection. Besides their function as gene delivery vehicles, lentiviral vector backbones containing the cis-acting sequences necessary to perform a complete replication cycle in the presence of vir Read More

Gene transfer into hematopoietic cells is currently being used to modulate immune responses, to protect hematopoietic cells against cytotoxic drugs or viral genes, and to restore gene deficiencies due to either inborn genetic defects or acquired loss of regular gene function. In particular, gene addition strategies for inherited severe combined immunodeficiencies (SCID) due to adenosine deaminase (ADA) deficiency or def Read More

Gene-engineered dendritic cells (DC) are being tested in cancer immunotherapy. DC are the best equipped antigen-presenting cells (APC) to overcome tolerance / ignorance to self antigens presented by cancer cells. Genetic immunotherapy with DC engineered to express tumor antigens has the potential advantages of endogenous epitope presentation by both major histocompatibility complex (MHC) class I and II molecul Read More

Bone marrow-derived dendritic cells have been used to treat established experimental tumors by unleashing a cellular immune response against tumor antigens. Such antigens are artificially loaded onto dendritic cells' antigenpresenting molecules by different techniques including incubation with synthetic antigenic determinants, tumor lysates or nucleic acids encoding for those relevant antigens. Ex vivo gene transfer with vir Read More

A variety of adoptive cellular strategies, aimed at boosting the immune system, have been tested in the management of metastatic diseases. Despite the drawbacks associated with ex vivo cell manipulation and upscaling, several such approaches have been assessed in the clinic. The use of lymphokine-activated killer (LAK) cells, autolymphocyte therapy (ALT) and tumor-infiltrating lymphocytes (TIL) have been the best stu Read More

Muscle is a convenient and accessible site for non-viral gene delivery, which can manufacture gene products and provide a long-duration of gene expression. The level of gene expression after administration of naked DNA plasmid or polymer-formulated DNA plasmid containing a reporter gene to muscle via syringe injection, however, is very low. As a result, no significant therapeutic effect can be detected after saline- or polyme Read More