Cancer Gene Therapy

Many human diseases are caused by inherited or acquired abnormalities in gene expression or regulation. Gene therapy was developed as a means of restoring lost or blocking abnormal gene functions. Unlike conventional therapies, gene therapy for cancer promises specific targeting of cancer cells with fewer toxic effects. The hope is to cure cancer.

Despite the presence of cancer associated antigens, cancer cells are poor immunogens. Anti-cancer immune response can be enhanced by increasing cancer cell immunogenicity or boosting effector (immune) cell performance. Not until recently, this aim can be reached by introducing genes into cancer or effector cells, an approach known as transgenic immunotherapy. This approach includes cancer vaccines, cancer infiltrating lymphocyte adoptive immunotherapy, lymphocyte cancer homing, and antibody-dependent cell-mediated cytotoxicity (ADCC).

Cancer Vaccines

Recombinant cancer vaccines are generated by transfecting genes into cancer cells. Such vaccines elicit an immune response to the primary cancer as well as a systemic anti-cancer response with immune memory. The technique involves primary culture of the cancer cells, ex vivo transduction of the cells with the selected gene, UV irradiation the genetically modified cells, and reinjection of these cells back into the patient. There are three different types of genes used for this purpose.

Tumor-Suppressor Genes

Loss of cancer-suppressor genes has been recognized as a cause of cancer. p53 is probably the best-known tumor suppressor gene. Approximately 50% to 60% of human cancers are associated with a mutated p53 gene or lack of p53 expression. p53-deficient cancers are often resistant to therapy. Restoration of wild-type p53 expression led to inhibition of cell growth, selectively inducing apoptosis of cancer cells, sensitization of cancer cells to chemotherapy and radiation therapy, decreased metastasis, and prolonged survival.


A proto-oncogene is the normal, cellular equivalent of an oncogene that is usually a gene involved in the signaling or regulation of cell growth. A single mutant allele or oncogene is sufficient for malignant transformation. Abnormal functions of oncogenes can be turned off by correcting the mutant genetic sequence itself or interfering with its expression. While it is difficult to correct the mutant sequence direct, blocking genetic expression might be accomplished through antisense sequences or ribozymes targeted specifically to the oncogenic messenger RNA. Antisense oligodeoxynucleotides against c-myb, c-muc, H-c-ras, bcr/abl, PCNA, CDC2, and EGF-related growth factor have been shown to inhibit cancer cell growth.
Walther, W. (Editor), Stein, U. (Editor). (2000) Gene Therapy of Cancer : Methods and Protocols (Methods in Molecular Medicine, 35). Humana Press.