Abstract
The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.
Highlights
Cancer represents a significant health burden, especially in developed countries, and one of the priorities of the medical sciences is to find new and more targeted therapies
The overall objective for cancer immunotherapy is to enhance tumour-associated antigen (TAA) presentation to effector cytotoxic T cells, and gene therapy techniques can be used to manipulate the functions of anti-tumour effector cells
These transgenes can be efficiently processed for class I antigen presentation, so that the particular HLA type of the patient would not be necessary for the TAA design
Summary
Cancer represents a significant health burden, especially in developed countries, and one of the priorities of the medical sciences is to find new and more targeted therapies One of these strategies has utilized gene therapy techniques to enhance the natural anti-tumour activities of the immune system. The first gene therapy human clinical trials that could be considered a clinical success were performed with -retrovirus vectors, exemplified in the study published in 2000 by Cavazzana-Calvo [9] They successfully corrected severe combined immunodeficiency (SCID)-X1 in 11 children using a mouse leukemia virus-based vector (MLV) as the gene transfer vehicle. The integration of the therapeutic retroviral vector genome close to proto-oncogenes led to their upregulation in corrected T cells, resulting in uncontrolled T cell clonal amplification These serious genotoxic effects were not limited to this particular clinical trial and other serious outcomes have been observed at least for the correction of chronic granulomatous disease. Gene therapy is already being applied in human therapy and this will facilitate the application of virus vectors such as lentivectors for the treatment of human cancer [9,10]
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