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Article by: Erin Carpenter

6 innovations that can improve human health (part 2 of 2)


Here we continue our World Health Day top 6 innovations with the potential to improve human health countdown. If you missed part 1, you can find it here, where we kicked off our list with: (1) DNA Sequencing Technology; (2) Large Population-based Genetic Cohorts; and (3) DNA as a Storage Device. Prepare to be inspired as we continue with our final 3 topics below. Enjoy!

4. CAR T-Cell immunotherapy 

Historically, the available options to treat malignancy were restricted to surgery, chemotherapy and/or radiation therapy—often very obtrusive treatments for the patient. . Recently, a revolutionary form of immunotherapy called Adoptive Cell Transfer (ACT) was used to collect and genetically reprogram a patient’s own immune cells to recognize and kill cancer cells by adding a receptor that recognizes an antigen only found on tumour cells, and therefore only killing cancer cells.1 The most successful ACT therapy is CAR T-Cell therapy, the equivalent of “giving patients a living drug” as described by Renier Brentjens M.D. of Memorial Sloan Kettering Cancer Center.2 In 2017, two CAR T-Cell therapies were approved by the FDA for the treatment of children with acute lymphoblastic leukemia (ALL) and adults with lymphomas.3,4 CAR T-Cell therapy is a personalized medicine approach since a patient’s own T-Cells are genetically-modified. Additionally, CAR T-Cell therapy only needs to be given to a patient once since the modified T-Cells are able to propagate over time within the body, providing a lasting anti-cancer effect.2

5Gut microbiome influence on drug efficacy 

In contrast to CAR T-Cell therapy, which serves to rev-up the immune system, checkpoint inhibition immunotherapy acts to release the brakes cancer cells put on the immune system5. Although there are a number of checkpoint inhibitors clinically available, the rates of success vary widely6. Why does the same immunotherapeutic drug produce a strong response in some patients, but not others? Earlier this year three studies were published in Science that illustrated the influence of the gut microbiome on the efficacy of immunotherapy drugs. These studies, led by Thomas Gajewski at the University of Chicago, Jennifer Wargo at the University of Texas MD Anderson Cancer Center, and Laurence Zitvogel at the Gustave Roussy Cancer Campus, basically characterized intestinal bacterial species as ‘good’ or ‘bad’ depending on whether they were present in patients that responded to cancer treatment7. Patients with a greater proportion of good bacteria responded better to checkpoint inhibition and experienced a longer remission than patients with more bad bacteria. In tumour samples taken from patients with more good bacteria, there were more immune cells that were able to recognize and destroy cancer cells, whereas in samples from patients with more bad bacteria there were more cells suppressing the immune system and causing the treatment to be ineffective.8,9 Additionally, use of antibiotics prior to immunotherapy that disrupt the natural bacterial flora of the gut was associated with more negative patient outcomes.10 

6. Gene editing technology

With the advent of gene editing technology, the ability to add, remove or alter specific sequences of DNA in living cells became a reality. One of the most exciting gene editing tools is CRISPR-Cas9, an acronym for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-Associated Protein 9.11 CRISPR-Cas9 was first harnessed for use in eukaryotic cells in early 2013 by Feng Zhang of the Broad Institute of MIT and Harvard.12 This technology has the potential to facilitate research, including the rapid creation of transgenic murine models, as well as potentially cure genetic-based diseases.13 In fact, the Switzerland-based biotech company Crispr Therapeutics has applied for permission to test a gene editing product in patients suffering with beta-thalassaemia and sickle cell disease—both inherited blood disorders. Similarly, the US-based company Editis Medicine is working on a gene editing product to treat a rare form of congenital blindness.14 This gene editing tool can also be used in epigenetic studies, as demonstrated in a 2015 study by Charles Gersbach and colleagues of Duke University, by adding acetyl groups to histones at specific spots in the genome causing an alteration in the expression of targeted genes.15 In 2017, a gene-editing experiment on embryonic human cells was published in Nature using the CRISPR-Cas9 tool to correct a mutation in the MYBPC3 gene which causes hypertrophic cardiomyopathy, and is the leading cause of sudden death in young athletes.16 Very recently a new form of the CRISPR system was discovered that specifically targets RNA using the Cas enzyme Cas13b.17,18 The ability to edit genes unquestionably has the power to the change the course of the human race.

We hope you enjoyed this second part of this series and reading about our final 3 highlights. Subscribe to this blog to be sure to get all future articles as soon as they are published.

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1. Guthrie, Greg. “CAR T-Cell Immunotherapy: The 2018 Advance of the Year”. net. American Society of Clinical Oncology (ASCO), January 30, 2018. Accessed 18 Apr 2018.

2. “CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers”. National Cancer Institute (NCI). National Institutes of Health (NIH). Accessed 18 Apr 2018.

3. “KYMRIAH (tisagenlecleucel)”. S. Food and Drug Administration (FDA). U.S. Department of Health and Human Services, 19 Apr 2018. Accessed 18 Apr 2018.

4. “YESCARTA (axicabtagene ciloleucel)”. )”. S. Food and Drug Administration (FDA). U.S. Department of Health and Human Services, 20 Feb 2018. Accessed 18 Apr 2018.

5. “Cancer immunotherapy”. What is biotechnology? Accessed 18 Apr 2018.

6. NCI Staff. “Gut Bacteria Influence Effectiveness of a Type of Immunotherapy”. National Cancer Institute (NCI). National Institutes of Health (NIH), 5 Feb Accessed 18 Apr 2018.

7. Kaiser, Jocelyn. “Your gut bacteria could determine how you respond to cutting-edge cancer drugs”. American Association for the Advancement of Science (AAAS), 2 Nov 2017.

8. Gopalakrishnan, V. et al. “Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients”. Science, 359, no. 6371, pp.97-103, 2018. doi: 10.1126/science.aan4236.

9. Matson, Vyara et al. “The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients”. Science, 359, no. 6371, pp. 104-108, 2018. doi: 10.1126/science.aao3290.

10. Routy, Bertrand et al. “Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors”. Science, 359, no. 6371, pp. 91-97, 2018. doi: 10.1126/science.aan3706.

11. “What are genome editing and CRISPR-Cas9?”. Genetics Home Reference. S. National Library of Medicine, 17 Apr 2018. Accessed 18 Apr 2018.

12. Cong, Le et al. “Multiplex genome engineering using CRISPR/Cas systems”. Science, 339, no. 6121, pp. 819-23, 2013. doi: 10.1126/science.1231143.

13. “CRISPR Timeline”. Broad Institute, 2018, Accessed 18 Apr 2018.

14. Crow, David. “crispr gene editing ready for testing in humans”. Financial Times. Genomics, 5 Mar 2018. Accessed 18 Apr 2018.

15. Ledford, Heidi. “CRISPR: gene editing is just the beginning. The real power of the biological tool lies in exploring how genomes work”. Nature, 7 Mar 2016. Accessed 18 Apr 2018.

16. Ledford, Heidi. “CRISPR fixes disease gene in viable human embryos”. Nature, 548, no. 7665, pp. 13-14, 2017. doi: 10.1038/nature.2017.22382.

17. Goldsmith, Paul. “Researchers harness novel RNA-targeting CRISPR system”. Broad Institute, 5 Jan 2017. Accessed 18 April 2018.

18. Smargon, Aaron A. et al. “Cas13b Is a Type VI-B CRISPR-Associated RNA-Guided RNase Differentially Regulated by Accessory Proteins Csx27 and Csx28” Molecular Cell, 65, no. 4, pp. 618-630.e7, 2017. Accessed 23 Apr 2018. 

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