Who would like to hear some really good news? Thought so. One of the promises of the molecular biology and genomics revolutions was that gene therapy – replacing defective, disease-causing genes with functioning ones, or otherwise treating these diseases by genetic means – would become a reality. Even, optimistically, something commonplace. Like so many things, however, it has proved more complicated than hoped, and those longed-for treatments elusive. There has never been a therapy of any kind that alters the disease progress of a neurodegenerative disease – until now. Continue reading
After my somewhat depressing previous post, I decided to comment on something a little more optimistic this time around, namely the success in getting treatments for some of world’s most underfunded diseases afflicting the world’s poorest people. And at a knockdown price, too… Continue reading
Sometimes the science of the future seems very far away, and sometimes it seems to happen almost faster than you would think. Immunotherapy is taking off at a record pace in the search for better cancer treatments.
The National Institute for Clinical Excellence (Nice), the body in the United Kingdom that licences medicines for use, has just approved a combination of two immunotherapy drugs in record time. These two drugs are ipilumab and nivolumab, which I blogged about as a treatment showing promising clinical trial results only a short while ago.
Nivolumab blocks a molecule secreted by cancer cells that prevents the T-cells of the immune system from recognising and destroying them. Ipilumab, which was approved by Nice in 2012, stimulates the T-cells to multiply. This drug combination has been approved for the treatment of metastatic (i.e. spread from its original site) melanoma, a particularly intractable cancer to treat. The life expectancy for this type of cancer is only around two years: the combination treatment has extended this to as much as ten years (and counting, in some cases). Moreover, ipilumab alone is effective in about 20% of cases: the combination raises that to 60%. So these are massively improved odds. I expect to see more successes soon, and, as more experience is gained with these exciting new techniques, hopefully the side-effects will become more manageable as well.
It’s been a busy couple of weeks, with a teething baby eating my sleep and job applications eating my time, so a longer written piece is off the cards for now. It seems my piece on new cancer treatments, specifically immunotherapy, however, was a timely one, as it’s hitting the news again, with big successes reported in the use of modified T-cell therapy to treat blood cancers, reported in the Guardian here. These include some startling trial results:
In the most promising study, about 35 patients with ALL were treated with Cars-modified T-cells; 94% went into remission, though symptoms could reappear. More than 40 patients with lymphoma have also been treated, with remission rates of more than 50%. In a group with non-Hodgkin’s lymphoma, there was evidence of diminished cancer symptoms in more than 80% of cases.
These are really impressive figures. Is it just hype? These results were reported at a major scientific meeting, and the ALL (acute lymphoblastic leukaemia) trial results are described as being under review and pending publication. So it’s not just a press release from a laboratory that has been wildly spun out of all proportion by an over-enthusiastic press. I for one will definitely be wanting to read the original research paper when (if) it is published. We can expect to see a flood of trial results and papers published within the next couple of years, if it lives up to even half of its original promise.
How often do you hear a new medical treatment, or any scientific or technological innovation, as “It sounds like something out of science fiction but WonderDrug X will cure Deadly Disease Y….” ? Too often, in my humble opinion, and, in my suspicions, by people who don’t read that much science fiction (or fact). But there are some cancer treatments coming up that have been mooted (or at least something similar has) in science fiction. Let me throw some catchphrases at you: “Personalised medicine”, “Biological therapy”, and, best of all, “Nanobots!!!” Which obviously deserve three exclamations all of their own. Amidst the headline tags, there’s a welter of confusing terms: “Targeted therapy”, “Immunotherapy”, “Oncolytic therapy,” “proton beam therapy,” and, my personal favourite, “Cyberknife”. Now I’ll go through some of the newer cancer treatments that come with these labels attached: some in use, some in development, and see if they do the justice hype – and if science fiction really did say it all first.
Following on from my post on the new treatment for ALL, I thought I’d go into cancer in general a bit more. In this first part of a double post, I’ll briefly go into what cancer is and the principles of the main types of current treatments. In the second part, I’ll consider some of the more futuristic cancer treatments that are starting to enter the mainstream.
News recently came out that a baby girl has been successfully treated for a particularly aggressive form of acute lymphoblasic leukaemia (ALL) using a form of gene editing. This is only the second time that gene editing has been used in people. The first involved modifying T-cells in HIV sufferers to make them more resistant to the virus, however, which was a far lower risk strategy as these people were not at imminent risk of dying.
ALL is a cancer of one of the two types of blood cell; the “white” ones, called lymphocytes, which fight infection. They are all produced in the bone marrow; a source of those famous stem cells: these are progenitor type cells that have the potential to multiply themselves (self-renewing) and for their offspring to differentiate into more than one type of cell. In the case of ALL, the stem cells for the white blood cells start multiplying uncontrollably, releasing lots of immature “blast” cells into the bloodstream. This reduces the number of red blood cells needed to carry oxygen, and also the number of mature white blood cells, so the body’s ability to fight infection is actually reduced. Treatment usually involves a combination of radiotherapy and chemotherapy to kill the cancerous cells (these techniques kill rapidly dividing cells – a hallmark of cancer cells and the major way treatments have traditionally targetted cancer cells – I will probably provide an overview of the principles of cancer and methods used to treat it in a later post; in the meantime, here is a useful link)
Essentially, what the researchers did was to take a type of immune cells (T-cell lymphocytes) and genetically engineer them using TALEN® proteins, which act as so-called “molecular scissors”; these cut double-stranded DNA and use the cell’s own repair mechanisms to join the gap, with your gene of choice inserted. In this case, an extra gene for a receptor called CAR19 was added. A receptor, incidentally, does exactly what it says on the tin; they are proteins that sit on the outside of cells and receive proteins that act as signals. In this case the signal was in the form of another protein, called CD19, that the ALL cancer cells have on their surfaces. The T-cells (called UCART19 cells) are then programmed to seek out and destroy the cancer cells. So far, so good, and there are several human trials underway for this. But there was one major snag – ordinarily, the T-cells to be engineered are harvested from the patient’s body, engineered, and put back, but in this case the patient was too small and ill to have enough to modify. What about using T-cells from a donor then? Great, except that these cells will be recognised as not belonging to the patient’s body, and destroyed by the immune system. In fact, leukaemia patients are given drugs that essentially destroy their immune system (as it is these cells that are cancerous) and so this shouldn’t be a problem – but one of the drugs also destroys donated T-cells. So, the team, led by Prof Qasim, did something rather clever, and used the TALENs to disable a second gene in the donor T-cells, which made them invisible to this drug.
One infusion (one!) of these cells essentially cured Layla of her cancer. Later on, she was given a full bone marrow transplant as her own immune system had been destroyed by all the cancer treatment. This means, incidentally, that none of the circulating donor UCART19 cells remain. And neither, all being well, do any cancerous cells at all.
This is more than just a neat solution to a problem specific to a particular patient: it is possible (and, indeed, is the aim of the Cellectis, the company that makes them) that T-cells could be engineered such that they are suitable for anybody, and could be an off-the-shelf treatment for these types of cancer, which holds great promise for future cancer treatments.
For more on the story, read GOSH’s press release here
For more on gene editing, Wikipedia has a link here