11.2.2.2 Immunotherapy

Another way for cancer gene therapy is to protect blood hoemopoietic stem cells from the effect of chemotherapy.  Generally, resistant lines arise due to the production of high level of multiple drug resistance (MDR) proteins, which pump toxic drugs out of the cell. Meanwhile the hoemopoitic stem cells naturally produce very low levels of MDR and are killed by low concentrations of toxic drugs. This resistance could be overcome by increasing the initial concentration of drugs to kill the cancer cells before resistant lines arise.  Gene therapy approach was carried out to increase the expression of MDR in hoemopoietic cells. Recombinant retrovirus can be used on hoemopoietic stem cells (Roth,. and Cristiano, 1997).

A second way for the immune system to fight cancer is to increase its sensitivity to cancer cells.  The immune system in man can recognize the cancer cells and kill them but in well-established cancer, the system fails to do this.  A method was developed to stimulate the production of cytokine that stimulate cell-mediated immunity.  The latest version of this treatment is to produce the cytokines in the cancer cells.  This stimulates the immune system, but in the vicinity of the tumour.

T lymphocytes play an important role in the host’s immune response to cancer. Modern cancer immunotherapies are designed to induce T cell reactivity against tumour antigens. To stimulate the immunoresponse investigators used cytokine genes. They developed a vaccine consisting of tumour cells transduced with cytokine genes. Therefore it is now possible to transfer cytokine gene directly into tumours in vivo (Tuting, et al 1997, Jaffee.& Pardoll. 1997).

A number of cancers have mutations in tumour suppressor genes such as p53. The p53 gene encodes a nuclear protein that acts as a transcriptional factor. Normally p53 is a tumour suppressor gene. Mutation of the gene would cause cancer.  It was found that when normal genes are introduced into cell lines from tumours carrying these mutations, the tumour characteristics disappear (Caplen, 1998, Clayman, et al 1998 and Roth, et al 1998).

Large number of clinical trials using gene therapy for different types of cancer are under progress, in eye cancer, retinoblastoma (Aldred, 1999 and Hayashi, et al 1999), breast cancers (Wicha, 1998), prostate cancer (Ficazzola and Taneja 1998).