Over the next five years a possible 900% increase in Gene and Stem Cell Therapy approvals has been forecast. Immunotherapies including checkpoint inhibitors and CAR-T cells have captured the attention of many scientists, physicians and cancer sufferers. The convergence of substantial incremental technical advances towards combined cell and gene therapy has led to improved clinical outcomes in immune deficiencies, haemoglobinopathies, blindness, immunotherapies and other inherited diseases. An audit of cell, tissue and gene products with marketing authorization in 2018 worldwide identified 44 unique products, 37 of them are cell and tissue therapies (84%) and mainly autologous (55%).
The challenge of realizing the full potential of genetic understanding has been in overcoming the hurdles of efficient gene therapy. Since the first human clinical trial using gene technology in 1989, there have been nearly 3000 approved clinical trials worldwide. The overwhelming majority of human clinical trials involves short-term gene expression or random integration of a therapeutic gene. Emerging technologies require controlled development in compliance with safety, regulatory and GMP requirements. More precise gene targeting tools were first described in the early 2000s. Targeted gene editing or replacement using Zinc Finger Nucleases or TALENS have been tested in about a dozen clinical trials since 2009. These include attempts to delete the CCR5 protein on T cells (completed 2015+) and therapeutic ZFN-mediated genome editing in mucopolysaccharidosis (recruiting 2016+) and the haemophilias (recruiting 2016+). The pace of clinical development has accelerated over nearly three decades of gene therapy. Within this context, its worth noting that the first ever (controversial) use of CRISPR to delete PD-1 in a lung cancer patient was administered in October 2016.
However, in parallel with objectively proven therapies, ‘stem cell tourism’ has become a billion dollar industry with increasing examples of false claims. Embryonic and induced pluripotent stem cells have been mired in controversy and clinical development has been forestalled. We reported an analysis of the global distribution of more than 400 unique businesses marketing stem cell-based interventions. Many of these online entities promote clinical applications of ‘stem cells’ beyond present-day standards of care. These data should be of immediate concern to governments and ethicist being lobbied to amend laws governing the manufacture, distribution and clinical use of human cell-based medical products. Unregulated, untested or unsafe stem cell ‘therapies’ place the field at a difficult crossroad. Blurring the lines that distinguish evidence-based cell therapies from those that are not remains a fundamental public health concern.