Oxford American handbook of oncology. Second Edition. Oxford University Press (2015)

Limited progress has been made in extending survival of patients with many types of malignancies through use of conventional cytotoxic therapies. Specific cancer-targeted therapies have been devised as a way of attacking the tumor microenvironment while avoiding systemic toxicities. Gene therapy for cancer represents the manipulation of genetic information in a way that affects the homeostasis of the tumor microenvironment for a therapeutic purpose. Such therapeutics may include the following:

  • Introduction of therapeutic genes that alter cell differentiation or survival
  • Genetic material that alters expression of genes or repairs somatic errors

The evolution of cancer gene therapy has evolved with expanding knowledge of the genetic changes associated with dysplastic and malignant transformation of normal tissues and with the development of improved technologies for genetic transfer.

In the United States, the FDA’s Center for Biologics evaluation and research (CBer) regulates human gene therapies that are considered biologics through the investigational new drug (IND) approval process.

  • A large number of phase I and II clinical trials have focused on gene therapy for cancer. However, there has not been an effective, safe therapy approved for commercial use in the United States.
  • Recently, gencidine, a recombinant adenovirus encoding p53, was approved for use in China and represents the first commercially available gene therapy product worldwide.

Gene therapy approaches generally fall under the following categories:

  • Correction of genetic error
  • Tumor suppressor gene therapy
  • Antisense, RNAi, or ribozyme correction of genetic error
  • Suicide gene therapy
  • Tumor microenvironment-targeted therapy (anti-angiogenesis, cytokine therapy)
  • Immunomodulation

Somatic correction of deficits and suicide gene therapy directed at tumors are thought to be more useful in the setting of minimal residual disease states. Immunomodulatory strategies seem useful in similar settings and can be employed in systemic or adoptive strategies.

Gene therapy represents a powerful tool in the quest to define effective immunotherapies for malignancies and represents one of the more important uses in the field.


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