Researchers from the University of California have managed to successfully engineer human T cells to detect and kill cancer cells, by using CRISPR technology.
Normal gene editing techniques make it hard to engineer T cells. It is not impossible, but when you attempt to add large DNA segments to the target cell using a vector you end up with toxic amounts of DNA. In contrast, electroporation of T cells with CRISPR proved to be an effective way to create edited T cells. Of course it wasn’t that simple, but the researchers after some tries managed to do this while also delivering large DNA fragments. When using CRISPR, a common concern is whether unwanted sequences in the genome will be targeted and whether those, if disrupted will harm the target. Thankfully for this experiment, the chances of any off-target modifications was low.
The first attempt to edit T cells for therapeutic purposes was done on patients with monogenic autoimmune disease, with abnormal IL2 genes. The modification targeted the IL2RA and demonstrated improved signalling function. This proves that not only this autoimmune disease but potentially all autoimmune diseases could be treated in a similar manner. By editing stem cells or even individual cells of the immune system it may be possible to treat such diseases or at least improve their symptoms. Although gene editing does have plenty of limitations and drawbacks, we are seeing more and more that we can indeed use it to treat some diseases effectively. Also, as the technology improves and we learn more, we will become better at controlling for various variables that may affect the success rate of such therapies.
The second attempt, targeted T cells, so that they can be programmed to target cancer cells. The T cell receptor locus of those cells was replaced with one that directed them to target cancer cells and mount on their antigens. This resulted in anti-tumour cell responses in vivo and in vitro. Those are great results and the way the experiment came out shows great promise. This is something that indeed should work in theory but experiments were showing average outcomes. Now, we see that with the right methodology such treatments are possible.
Of course it is still very early and we haven’t assessed yet the safety of such treatments. While editing specific types of cells might be safe, in vivo the results may vary and there may be side effects due to interactions with other tissues. Those results while promising, need further exploration.
The benefits of this therapy are plenty. While it may be expensive, requiring a lot of experts to work on a single patient for many hours, the work required could be done within a week, potentially saving lives in critical condition. The edits can be personalized if necessary, eliminating side-effects. There is no need for viral vectors and editing can be done to cells in-vitro and then introducing those cells in the patient’s body, thus improving safety.
This technology can be used to treat tons of genetic diseases by engineering cells to perform optimally if not. We can edit out unwanted genes and insert the right ones. Targeting mechanisms though are still required. While we can edit cells outside the body with electroporators, the same is hard in the patient’s body, and when it comes to organs for example, such processes might be impossible. Therefore, vectors, viral or not need to be made that can transfer CRISPR into specific cell types effectively without causing any unwanted side effects. Some potential technologies might include nanoparticles as we discussed last month on this article.
This study manages to prove that CRISPR delivered by electroporation can overcome issues of toxicity in T cells caused by viral vectors when attempting to edit large fragments of DNA. Additionally it proves that those technologies can indeed be used to make successful therapies in vitro and in vivo for both autoimmune diseases , by restoring IL2RA signalling and cancer by reprogramming T cells to target cancer cell antigens more effectively. Further studies should explore different non-viral methods for delivering such CRISPR molecules into T cells or even specific tissues in-vivo. Although such a thing is incredibly difficult, we have seen lately a lot of incredibly advancements in the field of genetics, showing overall great promise for gene therapy as a potential cure for many diseases.
I want to end this article as always, by asking you, the reader, to provide your opinion on the topic, let me and others know what do you think. I am sure that readers from different background will have different opinions and i am always excited to have a conversation on such topics. I see this study as great news. As someone who studied Biology and goes into Genetics, it shows promise for my field. Are you scared of such technologies or would you support these novel therapies? Let me know in the comments, on Facebook or Twitter where you can always Follow Qul Mind for science and tech news delivered daily.
Image: By Volker Brinkmann – (November 2005). “Neutrophil engulfing Bacillus anthracis”. PLoS Pathogens 1 (3): Cover page. DOI:10.1371. Retrieved on 2009-01-04., CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=2107792