CRISPR Clinical Trials for Cancer and Blood Disorders

For several years CRISPR gene editing has been a hot topic in pre-clinical research, with excitement growing as the technology enters the first set of clinical trials in the U.S. with the aim of treating cancers and blood disorders.

The treatment involves removing the patient’s own cells, using CRISPR to edit the faulty gene/insert a functional gene in vitro and injecting this back into the patient. This treatment aims to reduce the risk of rejection associated with non-autologous transplantation. CRISPR-editing is also aimed as a curative treatment rather than symptom management as the ‘edit’ is passed on to new cells during propagation.1

One person in the U.S. has already undergone treatment for sickle-cell disease by inserting the gene for fetal hemoglobin, to compensate for the defective protein.2,3 Information gathered from these trials will assess the long-term efficacy of CRISPR-editing and any side effects of the therapy. A similar treatment for beta-thalassemia in Germany is already showing promising results, with edited cells producing enough functional protein to negate the need for blood transfusion for over four months.2

More controversial trials where CRISPR gene-editing takes place in vivo rather than in vitro have also recently been approved by the U.S. Food and Drug Administration for the treatment of blindness in adults with Leber congenital amaurosis 10 4,5,6, though the trial has not yet started. However, ensuring the injected transfection vector reaches target cells only has raised concern over possible side effects.7

In terms of cancer treatment, T-cells are being edited to target cancer cells. One person has been treated for multiple myeloma, and another for sarcoma at the University of Pennsylvania, Philadelphia, PA 8, with similar trials being held in China.9 Though CRISPR is renowned for its editing accuracy, there could still be a risk of off-target effects. Therefore, the results of these initial trials are eagerly awaited with positive results potentially trigging a new era in the treatment of genetic-related diseases.

  1. Mirza z and Karin S. Advancements in CRISPR/Cas9 technology-Focusing on cancer therapeutics and beyond. Seminars in Cell and Developmental Biology 2019. S1084-9521(18)30113-7. doi: 10.1016/j.semcdb.2019.05.026.
  2. CRISPR Therapeutics press release July 2019 [Internet]. CRISPR Therapeutics Provides Business Update and Reports Second Quarter 2019 Financial Results. Available: Last accessed 16/09/19.
  3. Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics (2019). A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell Disease. Available: Last accessed 16/09/19.
  4. Allergan and Editas Medicine, Inc. (2019). Single Ascending Dose Study in Participants With LCA10. Available: Last accessed 16/09/15.
  5. Maeder ML, Stefanidakis M, Wilson CJ, Baral R, Barrera LA, Bounoutas GS, et al. Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. Nature Medicine. 2019; 25(2):229-233. DOI: 10.1038/s41591-018-0327-9.
  6. Editas Medicine, Inc Press Release 2019 [Internet]. Allergan and Editas Medicine Initiate the Brilliance Phase 1/2 Clinical Trial of AGN-151587 (EDIT-101) for the Treatment of LCA10. Available: Last accessed 16/09/19.
  7. Collins FS, and Gottlieb S. The Next Phase of Human Gene-Therapy Oversight. New England Journal of Medicine. 2018; 379:1393-1395 DOI: 10.1056/NEJMp1810628
  8. University of Pennsylvania, Parker Institute for Cancer Immunotherapy and Tmunity Therapeutics (2019). NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells). Available: Last accessed 16/09/19.
  9. Chinese PLA General Hospital (2018). Study of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Mesothelin-directed CAR-T Cells in Patients With Mesothelin Positive Multiple Solid Tumors. Available: Last accessed 16/09/19.

Written by Sumayya Nafisa Khan & Tom Southgate