Cancer Gene Therapy

Gene therapy is the insertion of a functional gene into the cells of a patient to correct an inborn error of metabolism or function, to alter or repair an acquired genetic abnormality, and to provide a new function to a cell. Cancer gene therapy employs gene delivery technologies to express desired proteins for combating the tumor cells.

Table 13. Gene Therapy-Based Cancer Drugs

P53 is a normal constituent of cells and is known as a tumor suppressor because it provides a powerful halt signal on cell growth. However, the P53 gene mutation in tumor cells results in the loss of tumor suppressor function and uncontrolled tumor cell growth. Advexin, adenoviral p53 gene therapy, supplies p53 protein in very high concentration in cancer tissue and restore p53 function, which selectively kills cancer cells while not harming the surrounding normal cells. Advexin combines the p53 tumor suppressor with a nonreplicating and nonintegrating adenoviral delivery system. Gendicine employed modified adenovirus serotype 5 expressing human normal p53 tumor suppressor gene. It was approved by the China State Food & Drug Administration (SFDA) and is the first commercialized gene therapy product ever approved in the world.

Melanoma differentiation associated gene-7 (MDA-7) functions not only as a tumor suppressor, but also as an immune enhancing cytokine. INGN241, adenovial MDA-7 protein gene therapy, expresses MDA-7 protein. The expressed MDA-7 protein is active and has a wide area of biological effect on cancers.

Many other gene therapy approaches are pursued for cancer treatments, inserting a "sensitivity" or suicide' gene into the tumor, for example by introducing the gene that encodes HSVtk; blocking the expression of oncogenes, for example by introducing the gene that encodes antisense K-RAS message; protecting stem cells from the toxic effects of chemotherapy, for example by introducing the gene that confers multiple drug resistance gene (MDR-1); blocking the mechanisms by which tumors evade immunological destruction, for example by introducing the gene that encodes antisense insulin-like growth factor-1 (IGF-1) message; killing tumor cells by inserting toxin genes under the control of a tumor-specific promoter, for example the gene that encodes diphtheria A chain.