Fighting cancer with CRISPR


Now we have staff writer Jennifer cousin Frankel. She wrote a story this week on Crisper and cancer immunotherapy to big ideas says mushed together for the first time in human patients. Hi Jennifer Hi. Thanks for having me sure. I said something scary. It's not every day that we get to say a something is a first. There's always a lot of pushback whenever we put it into a story or if it comes up in a research paper but this is some type of I. This is the first time that that researchers have reported on taking immune cells in this case the T. cells which we kind of think of as the soldiers of the immune in system that fight off infection using crisper to modify them together and then putting them back inside a human body and seeing what happens. It's that hasn't been done before. It hasn't been described before their trials that are going on. That are testing this and this is why we never put I in a headline exactly far to do was dive into the techniques. We're GonNa talk about cancer immunotherapy and then we're also going to talk about crisper. We need to kind of understand both of those things to understand what happened in this paper. This is a specific kind of cancer. Immunotherapy right yes. That's right so cancer. Immunotherapy is essentially trying being to harness the immune system to fight cancer. And it's something that's been really hot in the cancer field for the last several years in fact won the Nobel prize is just the other year. What this study is making use of is one technique in cancer? Immunotherapy that uses the T. cells and it tries to to sort of help. The t cells recognize tumor cells and then destroy them some of the problems that have come up as people have experimented with that. Were things like it. It doesn't really get into solid tumors and some other things. This is still a really new field and people are still working very hard to improve. Its success it's been pretty successful in blood cancers leukemia in lymphomas and there are two Cardi cell therapy's that companies have developed in that have been approved there are some additional additional hurdles in solid tumors. And it has been more difficult to consistently get the therapy to work in solid tumors solid tumors or things. Like brain tumor pancreatic host humor. Like I think yeah any tumor. That's kind of a solid mass as opposed to in the blood. That's the cancer immunotherapy side of things. Let's talk about the crisper side of things. Can you just tell us what crisper is. And then maybe we can talk about how. It's been used their politically or not so far. So crisper is another really hot area in biology Jay. It's a technology that essentially cuts DNA and then the DNA can kind of recombine in different ways it can be used in different settings to add genes or DNA to remove them. It depends but it can give a lot of flexibility around modifying DNA A and it's used in all different settings not just in medicine but strongly medicine is one area where there's been a lot of interest in using crisper because it's a way of modifying lying. The genome in this case crisper is used to modify immune cell so they took immune cells out of a patient and then use this gene editing technique to make changes to them. They had these three patients and what they did was they took out blood cells and then they modified those cells in the lab. They had to add in a gene gene. That was going to target a protein that was on the surface of their cancer cells. The other thing that they did was they used crisper to edit the genome such that they were knocking out three other genes and the genes that they chose they chose because they I hope they would make the T. cells even more powerful. They hope they would help them. Hang around longer in the body more effective against the tumors than they reintroduce introduce those cells. They gave them back in. That whole process takes several weeks. It takes four to six weeks to from the time you take the blood out to the time you put the cells back in. They had to go through a number of layers to make sure that they were really doing everything safely and carefully. So what were they worried about when they reintroduced these cells into the body. One one question was just you know with these cells even survive right. He just kind of disappear which has been a problem. In general with some genetically modified t cells it can be hard good for them to kind of thrive in the body and these these were cells that had been modified in several different ways. Then of course another question is are they going to cause harm MHM if they do survive and one particular concern with crisper. Is that when you go in to do this. Editing you can have these off off target effects. Were you accidentally cause modifications to other DNA. That you weren't aiming for there was concern that that could happen then of course that's changing other. DNA in the T.. Cells who knows what effects that might have on the patients so those are the big two questions and then also you know they probably wanted to know if the people would get better. Everyone of course hoped that that it would help. These patients get better at the same time. The trial was not really designed for efficacy it was too small and it was also also so new and so they made certain choices in the very specific details of the treatment. They offered that improved safety. There were certain things they did did to try and make it less likely that the immune system of the patients would react in a sort of dangerous way to the cells but in doing so that could potentially elite reduced. How effective the treatment is you know the target that they picked on the cancer cells? They pick that specific target because there had been a number of trials targeting doing that with traditional therapy so they knew was probably a pretty safe target. But it may be isn't the best target unfortunately and as you might expect from. I'm talking about it. The patients did not recover from their cancer. Because of this therapy. What were some of the other results of the experiment that we can talk about now so I would say the results were that for the time for which they've been followed? The treatment appeared safe so far. Nothing scary happened nothing. There were no showstoppers. They saw some off target effects. But those off target effects didn't seem to cause any obvious harm to the musicians in the cells that had the off target effects. The percentage of cells with those effects seemed to kind of fade out over time about the target effects like the changes made to the T.. Cells of these patients. Were those persistent in the body. One thing that I think was quite heartening. Is that these. He sells really stuck around in a way. That other t cells going after this particular target haven't in other published studies and so they've they've lasted so far up to nine months and they're continuing to follow these patients and also when they took out the cells over months which they did did they would take blood from the patients and then look at the sells again it could get them back and study them in the lab and those sales were targeting cancer in the lab now like you say in the patients. The benefits were definitely limited. There were three people treated one of those people has since died and in the other to their disease has progressed and they are getting other treatments. MHM so the effects were limited. You know it can be hard to kind of know how to understand that on the one hand this is just three patients and so we were very very sick. And so if we're thinking about what's going to be an effective treatment you need to treat more people to really know and then again you're thinking about this. First Time in people have focused on safety safety from your story from boats. It really seemed like that people in this field were saying this is a step. This is getting us over a really big hurdle. Yes I think it's a step and I think it's kind of layering on the use of crisper onto this other area of cell therapy that have gotten so much interest interest in generated so much excitement cancer but also still have a lot of room to improve and it's a way of saying can we make better use is other technology. What's expected to happen next more of the same thing? Are they going to try to infer different targets. One of the exciting things about this field right now. Is there so much happening. And people have so many he different ideas for what they could try and there are a lot of different theories and we don't really know what's going to pan out and what's not and so there are a lot of different. The group's thinking about different targets different cancers other diseases of course to apply crisper to their companies. That are involved. They're just a lot of different ways. You could go with this but right now. There are other trials that are recruiting patients for crisper modified t cells else and some people. I talked to said you know. There are surely going to be many more trials opening in parts result of this study. What kind of of regulatory oversight was there for this is there a body that governs crisper studies? There's not a body that's specific to crisper but there is as a group called the recombinant DNA Advisory Committee which is a a panel that has traditionally vetted the safety and ethics of different gene therapy trials funded by the US government or other other funders and so this went through the review of that committee. which is colloquially known as the rack of the and also so went through you know a lot of review of the National Institutes of health a lot of review from the US Food and Drug Administration? You know as you can imagine anything new. Where you're you're genetically commodifying cells to a degree? You have four earn away. You haven't before writing them into people you have to be careful and of course you know. Everyone has hopes for this therapy in the years ahead. And because of that you have to be so careful when you're starting out. The hopes of a lot of people were pinned on gene therapies. His and yeah you know some early problems. Really put a damper on the field for a long time. Yes if something really terrible happens not only is that obviously terrible for that individual it has these ripple effects across the field and so I think the people running this trial. We're thinking of both of those things as they designed and pursued the study. Thank you so much Jennifer. Thank

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