9 - Current status of gene marking and gene therapy in oncology clinical trials

Summary

After much public, scientific, and regulatory debate, the first clinical trial involving gene marking was initiated on May 22, 1989. Less than seven years later, over 600 patients had been enrolled in clinical gene transfer/gene therapy protocols at numerous institutions around the world. About 70% of these trials have studied oncology patients, but trials treating inborn genetic disorders such as adenosine deaminase deficiency, cystic fibrosis, and famial hypercholesterolemia, and acquired diseases such as AIDS, are also under way (Table 9.1; for review see Miller, 1992; Morgan and Anderson, 1993; Crystal, 1995). The lack of any unexpected or untoward problems in the early trials has led to a profusion of gene marking/gene therapy protocols. In addition, the trend over time has been a shift from ex-vivo gene marking toward in-vivo gene therapy protocols. New protocols are now being approved more quickly by the appropriate regulatory agencies as the public, scientific, and regulatory communities have become more comfortable with this emerging technology. In fact the need for any special regulatory overview of gene therapy protocols is currently under review (Marshall, 1995).

Current clinical gene marker/gene therapy protocols in oncology can be divided into four broad groups based on the target cell population – that is, the type of cells being genetically modified (Table 9.2). The first group of protocols involves the genetic modification of tumor-infiltrating lymphocytes (TIL). Initial marking studies are addressing questions about TIL trafficking and the general safety of gene marking/gene therapy protocols.