Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night!
1. UK calls for discussion on human germline gene editing
This week, 5 UK’s agencies released a joint statement on human genome editing. Key quotes:
We will continue to support the use of genome editing in preclinical biomedical research as well as studies that progress and refine these technologies. Within the UK, this research may involve the use of somatic (non-reproductive) or germ cells, including human embryos up to 14 days old – within the confines of the HFE Act 2008 – where appropriately justified and supported by rigorous scientific and ethical review.
We also recognise, however, that there may be future potential to apply genome editing in a clinical context using human germ cells or embryos, though this is prohibited by law in the UK and unlikely to be permissible in other European jurisdictions at present. This raises important ethical and regulatory questions, which need to be anticipated and explored in a timely and inclusive manner as the basic research proceeds and prior to any decisions about clinical application.
This statement is a call for wide open discussion with possibility of future clinical applications in germline editing if research will justify it.
Interestingly, mass media interpreted it as a call for change current prohibitive law on clinical application of germline gene editing:
Britain may need to change its IVF laws to allow the genetic modification of human embryos so that scientists can use a gene-editing technique that could eliminate certain inherited diseases, leading biomedical organisations warn.
While the US has imposed a moratorium on the use of genome editing of human embryos, the joint statement implies that the day might soon come in the UK when it is ethically justified to implant the first genetically modified embryo in a womb.
2. CART cell therapy news
A few very exciting news came up this week from booming CAR T-cell therapy field. First, publication of clinical study from Upenn team – long-term follow-up in CLL:
The overall response rate in these heavily pretreated CLL patients was 8 of 14 (57%), with 4 complete remissions (CR) and 4 partial remissions (PR). The in vivo expansion of the CAR T cells correlated with clinical responses, and the CAR T cells persisted and remained functional beyond 4 years in the first two patients achieving CR. No patient in CR has relapsed.
Importantly, this summer the first patient on CLL trial, celebrated 5-year tumor-free survival mark. Also read a blog post by Derek Lowe on this study.
The second news was about 2 studies, which described generation of so-called “affinity-tuned” CART cells. Playing with sensitivity (affinity) of T-cells to tumor antigens, researches were able to design low-affinity CARs, which allow to spare normal cells and selectively eliminate tumor cells. The approach was used by 2 different research groups on 2 solid cancers EGRF and ErbB2. Also read a blog post by AACR on these studies.
Finally, French company Cellectis announced strategic alliance with MD Anderson Cancer Center on clinical development of their allogeneic CART cell therapies in 5 targeted indications. To my knowledge, this is the first big industry-academia deal on allogeneic universal CARTs.
3. Use of liver-on-chip unveiled side effects of Tylenol
Organ-on-a-chip technology is starting to yield first significant clinical results. It was recently reported that implementation of liver-on-a-chip in discovery of unexpected toxicity of pain/ fever relief drug acetaminophen (well known as Tylenol). The results of the study were published in Archives of Toxicology. The authors demonstrated that much lower, considerably “safe” dose of acetaminophen causes severe hepatic toxicity. It’s not clear, as of now, how manufacturers and regulators will react, but impact of this study could be big. It was collaborative project between Israeli’s Hebrew University and German’s Fraunhofer Institute.
4. Cell membrane deformation to ease gene transfer
Do you remember cell squeeze (SQZ Biotech) technology to increase efficiency of gene transfer? Recently, one more independent study described microfluidic device, where cells undergo deformation to boost efficiency of CRISPR/Cas9 gene constructs delivery:
We introduce and optimize a microfluidic membrane deformation method to deliver sgRNA and Cas9 into different cell types and achieve successful genome editing. This approach uses rapid cell mechanical deformation to generate transient membrane holes to enable delivery of biomaterials in the medium. We achieved high delivery efficiency of different macromolecules into different cell types, including hard-to-transfect lymphoma cells and embryonic stem cells, while maintaining high cell viability.
Looks like SQZ Biotech got a competitor. I asked SQZ Biotech on twitter about this study, but did not get a response.
5. Evasion of gene therapeutics from neutralizing antibodies
Neutralizing antibodies to AVV gene vectors is a big limiting factor in clinical gene therapy. A group of researchers figured out the way to avoid antibody reaction to AVV gene constructs:
The objective of this proof-of-principle study was to explore the possibility of isolating AAV mutants that evade NAbs and retain efficient tissue transduction to facilitate repeat administration in patients who were previously treated with AAV.
6. More on the first iPS cell trial suspension
Nicole Forgione wrote very interesting and thought-provoking post for the Signals blog on the recent news about suspension of iPS cell trial in Japan. Importantly, she brought such competing with iPS technologies as visual prosthetics and gene therapy:
This leaves us with the question, why the focus on iPSCs given that there are alternative approaches?
I also think, that such modern technologies as prosthetics and exoskeletons may be a serious competitors for cell therapy.
7. More on organoids
The Scientist has a very good overview piece on developments in organoids technologies. Interestingly, they asked different labs on technical challenges, considerations and approximate cost of the procedure. Generation of some research-grade organoids may cost as high as $150 USD per organoid and as low as $1. An excerpt about brain organoids:
Researchers studying neurodegeneration might consider examining their organoids starting at about four months. Although the organoids survive for up to 15 months, by that time they don’t look healthy. They start to decline at around six or seven months, as the neurons begin to disappear and are replaced by glia.
8. Collaboration on scaling up of autologous cell therapies
Bioprocess Online has very interesting post on industry collaboration between Lonza and Octane for development of scalable technology for autologous cell therapies:
As far as FDA approval goes, Dr. Smith says the Cocoon platform is not a medical device; it is used to produce a medical product and so the supporting data that is going to be necessary for submissions is something Octane can assist clients with. “Each cell-based drug that is approved has to go through a regulatory process for the product. Our system becomes part of the manufacturing process, so we are generating Master File information clients can use for submission with the different regulatory agencies.”
Good read for cell product developers!