Chapter 8 – Toxin-Based Cancer Gene Therapy: Under the Control of Oncofetal H19 Regulatory Sequences

Specific targeting of cancer cells while sparing normal cells with therapeutic mediators is a critical advantage over the current conventional drugs. Although various strategies can potentially be followed to achieve this vital goal, this review focuses on the strategy of transcriptional targeting of tumor cells by employing a toxin gene. Tumor-specific regulatory sequences can be used for this purpose to drive the expression of a toxin specifically in tumor cells. It is of immense importance to choose regulatory sequences of a gene that is playing critical roles in various aspects of tumorigenesis to increase the therapeutic window. It would be beneficial to identify a strong cancer-specific promoter for treating a wide range of cancers while having minimal toxicity. In light of these prerequisites, we present our experience with the H19 gene and the successful use of its regulatory sequence to drive the expression of diphtheria toxin A in both preclinical and clinical studies.