Cancer Gene Therapy

Abstract

Overview The encouraging results of cancer gene therapies have increased their entry into mainstream oncological practice. Gene transfer or gene editing can modify the cellular phenotype and behavior of malignant cells or of host cells, thereby modulating tumor responses. In this article, we discuss both of the above approaches and describe the vector systems that are able to produce the intended genetic modifications. We describe current clinical successes of gene therapy and outline the challenges it has yet to overcome. The success of any gene therapy for cancer requires efficient, safe gene transfer with vectors that can either integrate into the human genome (e.g., retroviral, lentiviral, adeno‐associated viral, or nonviral transposons) or remain largely or completely episomal (e.g., adenoviral, herpesviral, or nonviral plasmids). To date, genetic “correction” of consequential numbers of cancer cells has not proven feasible, but infectious cytolytic viral therapy, used with accompanying immunomodulatory genes within the oncolytic virus, is beginning to demonstrate an impact in the clinic. Enhancement of active cancer immunotherapy with forced expression of antigens and cytokines or the enhancement of adoptive immunotherapy by engineering T lymphocytes with specific T‐cell receptors and/or chimeric antigen receptors shows greatest immediate promise, although ultimately a combination of multiple approaches will prove optimal.