Cancer Gene Therapy II - Page 2© David Olle
Page 2
Feb 6, 2001
Stimulation of the Immune System
There are two basic assumptions underlying the use of gene transduction (transfer) for immunotherapy of cancer. The first assumption is that unique antigens specific to the cancer exist. In many instances they can be hard to find. The second assumption is that the immune system is intact, capable of recognizing the antigen, and mounting an attack against the cancer cell. Cancers thought to be most sensitive to immunotherapy include melanoma (skin cancer), renal cell carcinoma (kidney), colorectal cancer and non-small cell lung cancer.
Currently, the most active area of research involves introducing one of the cytokine genes into the cancer cell. As you will recall, cytokines are hormones secreted by the immune cells that serve to communicate with and stimulate other parts of the immune system. After the cancer cell receives the cytokine gene, it secretes large amounts of the cytokine, which in turn stimulate an immune response to an antigen present on the cancer cell.
There are several options to deliver the cytokine gene. The original method was ex vivo, or out of the body. Tumor cells are removed at surgery, grown in culture, transfected with the gene, and finally reinjected into the patient. A second approach is to introduce the cytokine gene into one of the viral or non-viral vectors previously mentioned. The vector is then injected directly into the tumor. Recently, there has been interest in transferring genes encoding tumor-associated antigens or cytokines directly into dendritic cells. Dendritic cells are necessary to trigger the immune response to foreign antigens. Since dendritic cells often do not recognize the antigens on cancer, the insertion of these genes may prime the cells into action.
It is well known that cytotoxic T cells must be stimulated by two signals before it can react to a cell as foreign. The first signal is the binding of antigen to a receptor on the T cell. The second signal is a molecule such as B7 that is produced by the infected antigen-presenting cell that encounters the T cell. This lack of a second signal is thought to be the reason for a lack of response to many cancers. A recent development involves the preparation of a plasmid vector containing genes for the two cytokines, interleukin-12 and interferon alpha. The interferon improves the expression of antigen on the tumor cell surface, while the interleukin provides a co-stimulatory signal. Chemosensitization 1 The strategy behind this technique is to introduce a gene into tumor cells that encodes a protein that converts an otherwise non-toxic pro-drug into a toxic substance. In effect, you are causing the cancer to commit suicide. Two genes currently under investigation code for enzymes that are not found in humans, so they are foreign.
Go To Page:
1
2
3
The copyright of the article Cancer Gene Therapy II - Page 2 in Cancer Treatment is owned by . Permission to republish Cancer Gene Therapy II - Page 2 in print or online must be granted by the author in writing.
|
