Techniques to introduce DNA into cells

♦ Lipid complexed with DNA

♦ DNA in lipid vesicles

♦ DNA in red blood cell ghosts

♦ Direct micro-injection of DNA

♦ Exposure of cells to high voltage

The non-viral methods are convenient and have an obvious safety advantage, but they have low efficiency and result in transient gene expression. On the contrary, viral (retroviruses, adenoviruses, poxviruses) vectors represent the most efficient, stable manner of integrating DNA into large numbers of target cells.

Based on the knowledge gained from other approaches of cancer immunotherapy, several strategies have been proposed for using gene therapies in patients with malignancies. Genes encoding for cytokines can be transferred in vivo to the tumour or to TILs. Alternatively, tumour cells or antigen-presenting cells (APC) can be genetically engineered ex vivo and re-injected in the patient to enhance tumour immunogeneity. Furthermore, genetic modification of immune effector cells may enhance their survival and increase their tumour recognition and anti-tumour efficacy, in vivo.

Clinical trials are being conducted in patients with pancreatic, lung, breast, prostate, and bladder cancer. These trials have demonstrated the feasibility and safety of genetic manipulations in cancer patients, although the clinical benefit from gene therapy is not clear. Attempts are currently focused on the development of techniques that would warrant the efficient gene delivery to selected tissues and control its expression, anticipating the mobilization of an effective anti-tumour immune response.

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