## The origin of cell therapy

The idea of using viruses as carriers – vectors for transferring DNA into human cells was implemented in the early 1990s, when a foreign gene was introduced into the human body for the first time. TIL lymphocytes(tumour-infiltrating lymphocytes), a class of white blood cells found in or in close proximity to tumours, were isolated and then transfected with a retrovirus carrying the NeoR gene. The product of this gene confers resistance to the antibiotic neomycin to the cell, which can subsequently be used for selection of the transformed cells and simultaneously as a marker for detection of cells with NeoR gene. After administration to the patient, the transformed cells were able to migrate in the body and reach their target, the tumour tissue (Figure 10.3).

The promising beginnings triggered a great wave of enthusiasm. This led to the first clinical trials and, unfortunately, also to the first tragedy. The victim was the then 19-year-old Jesse Gelsinger. Jesse suffered from a disease caused by a mutation in the gene for ornithine transcarbamylase (OTC), an important enzyme in amino acid and nitrogen metabolism. In his case, the disease had “mild” symptoms – he lived on supportive care and a strict diet. He volunteered for clinical trials in which he was administered gene therapy in the form of an adenovirus (ADV) carrying a healthy OTC gene. Although it was supposed to be a virus better tolerated by the immune system, an unfortunate combination of circumstances led to tragedy, and Jesse died as a result of the adenovirus infection. Over the course of a lifetime, people usually overcome several infections caused by ADV in the form of respiratory or digestive illnesses, usually with mild symptoms. This means that our immune system is highly likely to be able to respond quickly to repeated infections. This was apparently also the case with Jesse, who was given a very high dose of virus that likely led to an exuberant immune response. Four days after the therapy, Jesse's body collapsed. Because of this and several similar tragedies, the development of gene therapy has slowed down, with the main goal being to identify possible risks and find appropriate solutions.