First Clinical Trial of Gene Editing To Help Target Cancer (arstechnica.com) 23
An anonymous reader quotes a report from Ars Technica: Today, scientists are releasing the results of a clinical trial designed to test the safety of gene editing as a way of fighting cancer. The results are promising, in that a version of the CRISPR gene-editing system that's already a few years out of date appears to be safe when used to direct immune cells to attack cancer. But the cancers that it was meant to treat simply evolved ways of slipping past immune surveillance. For the clinical trial, this gene-editing system has been combined with recently developed immune therapies that target cancer. There is a class of immune T cells that kill cells recognized as foreign, either because they come from a different person (such as after an organ transplant) or because they are infected with a bacteria or virus. These cells can also recognize and attack cancer but often don't, in part because cancer cells are so similar to healthy ones. People have engineered versions of the T cells' recognition system that specifically target cancer cells, and placed these back into patients, helping the immune system attack the cancer, sometimes with spectacular results. As part of the clinical trial, gene editing was used to improve the efficiency of the cancer-targeting T cells. This was done in two different ways.
The first was to target a gene that normally functions to tone down the immune system (called PDCD1). There has been evidence generated in mice that using antibodies that block the protein made from this gene will increase the immune system's attack on cancers. For this work, the researchers targeted the CRISPR system to delete part of the gene itself, inactivating it. This poses a potential risk, as a failure to tone down the immune response can lead to problematic conditions such as autoimmune diseases. The other way gene editing was used was to knock out the T cell's normal system for recognizing foreign cells, called the T cell receptor (TCR). The TCR is composed of two related proteins that form a binary receptor complex. Engineered versions of this protein are the ones used to get cells to recognize and kill cancer. Normally, these engineered versions of the TCR are simply inserted into an immune cell, where both they and the cell's normal TCR genes are also active. The result is four different TCR parts active at the same time, resulting in a variety of hybrid TCRs. At best, these are ineffective and will reduce the total amount of active TCR in a cell. At worst, they'll cause the T cell to attack healthy cells. For the trial, the researchers generated CRISPR constructs that targeted the cell's normal TCR genes. When successfully deleted, this would ensure that the only TCR on the cell's surface would recognize cancer cells. The researchers ended up working with a total of three patients that had cancers recognized by a known version of the TCR genes.
"While the rates of successful editing were high, the procedure is nowhere near 100 percent effective, and rates of editing varied from nearly half down to 15 percent, depending on the gene," the report says. It adds: "There were no serious adverse affects of the T cell infusions, no sign of a problematic immune response, and the cells persisted in the patients up to nine months after the transfusions, indicating they were tolerated well. [...] The response to the tumor, however, was limited. Two patients appeared to stabilize, while the third showed a response in some tissues but not in others. Ultimately, however, the disease began to progress again, and one of the patients has since died."
The first was to target a gene that normally functions to tone down the immune system (called PDCD1). There has been evidence generated in mice that using antibodies that block the protein made from this gene will increase the immune system's attack on cancers. For this work, the researchers targeted the CRISPR system to delete part of the gene itself, inactivating it. This poses a potential risk, as a failure to tone down the immune response can lead to problematic conditions such as autoimmune diseases. The other way gene editing was used was to knock out the T cell's normal system for recognizing foreign cells, called the T cell receptor (TCR). The TCR is composed of two related proteins that form a binary receptor complex. Engineered versions of this protein are the ones used to get cells to recognize and kill cancer. Normally, these engineered versions of the TCR are simply inserted into an immune cell, where both they and the cell's normal TCR genes are also active. The result is four different TCR parts active at the same time, resulting in a variety of hybrid TCRs. At best, these are ineffective and will reduce the total amount of active TCR in a cell. At worst, they'll cause the T cell to attack healthy cells. For the trial, the researchers generated CRISPR constructs that targeted the cell's normal TCR genes. When successfully deleted, this would ensure that the only TCR on the cell's surface would recognize cancer cells. The researchers ended up working with a total of three patients that had cancers recognized by a known version of the TCR genes.
"While the rates of successful editing were high, the procedure is nowhere near 100 percent effective, and rates of editing varied from nearly half down to 15 percent, depending on the gene," the report says. It adds: "There were no serious adverse affects of the T cell infusions, no sign of a problematic immune response, and the cells persisted in the patients up to nine months after the transfusions, indicating they were tolerated well. [...] The response to the tumor, however, was limited. Two patients appeared to stabilize, while the third showed a response in some tissues but not in others. Ultimately, however, the disease began to progress again, and one of the patients has since died."
Irony (Score:1, Insightful)
Re: (Score:1)
It's intelligent design versus evolution, and everyone sane is rooting for design.
Excuse my stupidity, but I assume you are using 'intelligent design' cleverly as an ironic double entente, i.e., design by rational intelligence, rather than created by God*, like Yuval Noah Harari does in his book 'Homo Deus'. There, Harari suggests that gene editing is one of the things that, at some point in the future, will make truly better people. So much so in fact, those people will not be the Homo Sapiens we are today.
BTW, in a twist of fate, such technology may keep 'those people' from dying of a
Re: (Score:2, Funny)
God, extraterrestrial intelligence, or anything else
We could have been designed by a flying spaghetti monster. A giant fortune cookie from a parallel universe? There is no limit to insanity once you let imagination run wild.
Re: (Score:2)
It's intelligent design versus evolution, and everyone sane is rooting for design...
"Created by God" is design by a rational intelligence... You are proposing a distinction without a difference...Because reasons.
Associating 'rational intelligence' with an 'intelligent design' deity is just a belief, and while I could go into the fallacy of the Watchmaker analogy, BeauHD's article was about genetically engineering humans to fight cancer. So, if you will, we are starting to intelligently redesign humans in what may eventually produce our replacement, 'Homo Deus', who won't get cancer, die of old age, or even think the way we do.
Re: Irony (Score:1)
Re: Irony (Score:1)
Re: (Score:2)
Re: (Score:2)
This is getting very close to Humans as Gods.
Why is that a bad thing? Because it was bad in those Star Trek episodes?
Re: Irony (Score:2)
Re: (Score:3)
de móriens obliviscatur
This is bad Latin. Where did you read this? It doesn't make grammatical sense.
The preposition de demands the ablative, but moriens is in the nominative.
What are you trying to say?
You *might* mean moriente obliviscatur, with the ablative of agent.
My advice is to stop using Latin to try to sound intelligent if you don't have the faintest idea how it works.
Re: (Score:2)
This is bad Latin. Where did you read this? It doesn't make grammatical sense.
1) Go to Google.
2) Type in "Latin to English" and press Enter or click on 'Google Search'.
Wait for the next screen, with two boxes, one labeled 'Latin', the other 'English'.
3) In the box labeled 'Latin' put "de móriens obliviscatur".
What appears in the box labeled 'English' is "Forget about dying"; Considering what I wrote before, it's a relevant reply to the age-old aphorism "memento mori".
And no, I'm not good at Latin. English neither.
Re: (Score:2)
And no, I'm not good at Latin. English neither.
Then you should have written fuborgubet ubabubout dyubing instead. At least it would have been funny.
Re: (Score:2)
It would be more clever if you had saved the joke for an illness caused by an infection. Cancer doesn't evolve. It interferes with evolving.
Re: (Score:2)
Re: (Score:3, Informative)
Cancer does not evolve in quite the same way. Inside one patient, yes, his cancer can evolve. If you find a therapy that kills off 99% of his cancer cells while the remaining 1% are somehow resistant to it, those 1% will grow and the cancer will appear to have "come back and evolved" to resist the therapy.
But cancer as a disease in the population does not really evolve (except slowly in random directions without any evolutionary pressure in any way, like any other minor variation in our genome). Nature is n
Re: Irony (Score:1)
How do they avoid autoimmune disorder? (Score:3)
it seems to me that it is more correct to move in (Score:1)