Unlike many other medical approaches, cell and gene therapies (CGTs) have the potential to be a one-time cure treatment in the future for conditions like multiple, ALS, Haemophilia, Cystic Fibrosis, Cancer, HIV, MS and many more.
The concept of CGTs initially rose in the early 60s and early 70s and turning this concept into a therapeutic reality has taken an enormous amount of scientific discovery and innovative manufacturing efforts. Today in 2022, these therapies are slowly being approved by regulatory bodies.
What’s the difference between the two ?
Various diseases can involve a genetic component- multiple copies of a gene, a gene structurally defective or a missing gene. Gene therapy involves the transfer of genetic material to replace or modify genes to correct a deficiency, sometimes modifying an expression of a gene by turning it on or off or by altering the DNA sequence of the target. This can have a profound effect in congenital diseases where the disease is associated with malfunction of a single gene.
Cell therapy involves the transfer of cells with the appropriate/desired function into the patient. It can use cells from the person’s own cells (autologous) or another person (allogenic). The cells can be genetically altered or unaltered. This therapy is personalised to treat an individual’s condition, like CAR-T cell therapy whereby scientists take a person’s own cells and genetically modify them outside the body, increase the number of modified cells and then re-infuse these cells to produce a therapeutic benefit. Therapies like this can alter a patient’s cells so their immune system can then target and destroy previously dormant cancer cells. These cells are usually delivered in a vector or carrier leading the uptake of genes into the desired cells of the body.
The projected size of the CGT market is expected to be $14 billion by 2025 with 2000 open or planned CGT trials and 1-20 projects new approved CGT products in the US and separate estimates suggest that by 2030 half a million patients in the US alone will have been treated with 40-60 approved cell or gene therapy products.
One drawback to broad application of these novel techniques is the high cost of goods partly due to the complexity of manufacturing. A number of different components, including viral vectors, plasmids and cells comprise the final therapy products. Of course over time cost of goods will decrease with technological advancements, additional effort and innovative and inventive approaches. Improvements in delivery mechanisms, vectors and manufacturing are needed to make these therapies more cost effective and broadly available. Consortia involving industry participants, government and academia will be critical to these efforts.
For instance, vector systems which are more universal may improve the scalability of manufacturing. Such progress will also allow enhancements in the tissue specificity of the administered therapy. The lack of safe delivery systems that are both therapeutically and cost effective is a headwind to the application of CGT technologies.
Furthermore, advancements in nucleic acid engineering, molecular biology and nanotechnology may lead to novel non-viral vectors being developed that prevail over the limitations of existing delivery methods. In addition, today reverse genetics is not possible for almost all viruses and this vastly increased the virus types that can be evaluated as potential vectors. In addition to adeno-associated viruses (AAVs), herpesviruses , poxviruses and some non-human viruses are not being studied for their potential as gene therapy and vaccine vectors; some of these viral vectors may provide better efficacy profiles and safety compared to current delivery methods.
The capability to use allogenic rather than autologous donors will also allow for possible scalability of adoptive cell therapies. Advancements in patient stratification through the identification of more prognostic and therapeutic biomarkers may further improve CGTs by matching patients with therapies that minimize side effects and maximise efficacy.
In conclusion we can look forward to advances in these critical areas and a deeper understanding of disease biology to drive innovation and expansion of these modalities beyond current applications in oncology and rare diseases to other therapeutic areas and clinical indications. However, CGTs will continue to face new challenges around the evolving regulatory landscape, pricing and reimbursement, manufacturing and development. Despite these challenges, CGT products have already reached the market.