Gene Therapy Treatment

Gene Therapy and Cancer

• Cancer is caused by the somatic mutation of cellular genes. 
• These genes include oncogenes, tumor suppressor genes, and DNA repair genes.
• The generation of cancer is currently thought to be multi-step process of genetic alterations that vary according to the type and stage of cancer.
• Since cancer is a genetic disease, gene therapy could be applied in treatment of tumors. 
• The most advanced applications of gene transfer technology in medicine are in gene therapy for cancer. 
  
    Immunomodulation - Gene therapy:
  
  
• Cells of the immune system have been found to recognize specific antigens of tumors and mount both humoral and cellular responses. 
• During cancer development, this response is often limited in  intensity and duration. Strategies are being developed to reconstitute an effective antitumor immune response. Advancements in immunology have made Immunomodulation (immunological approaches to treatment) the most dominant strategy in gene therapy for cancer. 
• These approaches can be categorized in to three types according to target cells, mode of delivery, and transferred transgenes. 
• Target cells include tumor cells, T cells, host cells, APCs (antigen presenting cells), and others. Mode of delivery refers to choice of vector, in vitro, ex vivo, or in vivo).  Transferred transgenes refer to cytokines, co-stimulatory molecules, and tumor-associated antigens.
  
  Suicide Strategy
  
  
• The basic concept of using prodrug-converting enzymes is to limit the action of a known cytotoxic drug to local tumor areas. 
• Targeted prodrug therapy includes the delivery of a gene that activates a nontoxic prodrug to a cytotoxic product by using viral vectors. 
• This method maximizes toxicity at site of vector delivery while minimizing toxic effects on distant cells. 
• The cDNA of the enzyme is delivered in to the tumor by a vector.
• The corresponding nontoxic prodrug is applied and is taken up by tumor cells. 
• Since these cells have incorporated the cDNA in to their genome, they express the prodrug-converting enzyme.
• Therefore, when the cells take up the drug, it is converted in to a cytotoxic drug that kills the tumor. 
  
  Tumor Suppressor Genes and anti-oncogenes:
  
  
• Oncogenes, or genes that promote proliferation, become activated while tumor suppressor genes, or genes that terminate proliferation, become inactivated. 
• Approaches in this method include the inactivation of oncogenes or the re-constitution of tumor suppressor genes that have been inactivated by gene deletion or other mechanisms. The most effective procedure has been to target genes known to be dysfunctional. 
• The most targeted tumor suppressor gene has been p53  because it is the most commonly mutated gene.