Immunological Approaches for Gene Therapy of Cancer

Abstract

The identification of immunostimulatory and tumor antigen genes combined with advances in our ability to modify gene expression has fostered a new era of tumor immunotherapy. These novel immuno-gene therapies include tumor cell vaccines genetically engineered to express cytokine genes or modified by antisense vectors to inhibit immunosuppressive or differentiation factors, cytokine gene transfer into tumor infiltrating lymphocytes (TILs), intratumoral injection of allogeneic MHC or cytokine cDNA and vaccination with tumor antigen nucleic acids. Immuno-gene therapy is the most frequent form of gene therapy in current clinical trials. Table 1 lists the clinical trials which have been submitted for approval to regulatory agencies worldwide. Each of these novel immuno-gene therapies has advantages and disadvantages with respect to their potential for clinical applications. In general, immunotherapies involving autologous tumor cells have the potential advantage of containing the largest number of pertinent tumor antigens for a particular patient. However, the customized nature of autologous tumor and TIL-based treatments make them expensive and difficult to manufacture. The use of allogeneic cell lines in vaccine preparations provides practical advantages.