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Crispr Wins Key Approval to Fight Cancer in Human Trials

bloomberg.com

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Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#11

Post by unimpressive »

astazangasta wrote: post #9
melling wrote: post #6

Earlier quoted context omitted.

I assume that you haven't heard that immunotherapy is the new big thing in cancer research? It's how they cured former President Carter: http://www.forbes.com/sites/arleneweintraub/2015/08/21/jimmy...

I do cancer research at UCSF on an immunotherapy project...

I'm not one to usually complain about downvotes, but this is ridiculous. The HN hivemind at its most absurd.

This person is literally working in the research sector involved, giving their opinion (it's not a nice opinion, but it is presumably informed), and getting downvoted because the HN crowd doesn't like it.

EDIT: At the time I wrote this comment the parent comment and the root comment were both far into the negatives with downvotes.

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#13

Post by refurb »

astazangasta wrote: post #4

I'm calling it here, this trial will fail hard. The basic idea is this: the cancer has a number of mutations that produce novel antigens that don't exist in normal cells. If we can train T-cells to recognize these, they can attack the tumor with great specificity and kill those cells. The problem is, all the tumor has to do to evade this targeting is shed the problematic mutation, which is easily done - tumors are gr…

What about the CAR-T therapy that has work pretty well against blood cancers (ALL and CLL if I remember correctly)? Seems there were a handful of remissions in patients who had failed everything else.

What makes this approach so destine to fail? It's an honest question as I'm not as familiar with the details.

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#14

Post by return0 »

astazangasta wrote: post #7
return0 wrote: post #5

Earlier quoted context omitted.

How long will this process take? Is it enough to create a new therapy to target the mutated cancer?

People develop resistance to TKIs (tyrosine kinase inhibitors, the previous mode of therapy) within months; you could keep chasing the dragon, but the tumor is just going to keep doing the same thing, shedding whatever mutation you target. In this case you're not even targeting mutations that the tumor relies on (as you are with a TKI), so there's absolutely no fitness cost to the tumor to evade.

But what if the antigens are vital for the tumor ? What mutation are you referring to? Presumably the immune system will kill the cancerous cells ( shedding the mutation as well).

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#15

Post by megalodon »

unimpressive wrote: post #11
astazangasta wrote: post #9

Earlier quoted context omitted.

I do cancer research at UCSF on an immunotherapy project...

I'm not one to usually complain about downvotes, but this is ridiculous. The HN hivemind at its most absurd. This person is literally working in the research sector involved, giving their opinion (it's not a nice opinion, but it is presumably informed), and getting downvoted because the HN crowd doesn't like it. EDIT: At the time I wrote this comment the parent comment and the root comment were both far into the nega…

Agreed, people seem to be downvoting because they hope he/she's wrong rather than to post a reply explaining their reasoning. I see nothing wrong with the root comment and just upvoted it to give it more attention.

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#16

Post by return0 »

unimpressive wrote: post #11
astazangasta wrote: post #9

Earlier quoted context omitted.

I do cancer research at UCSF on an immunotherapy project...

I'm not one to usually complain about downvotes, but this is ridiculous. The HN hivemind at its most absurd. This person is literally working in the research sector involved, giving their opinion (it's not a nice opinion, but it is presumably informed), and getting downvoted because the HN crowd doesn't like it. EDIT: At the time I wrote this comment the parent comment and the root comment were both far into the nega…

Give it an hour or so. the hivemind is usually strong in the beginning.

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#17

Post by darawk »

astazangasta wrote: post #7
return0 wrote: post #5

Earlier quoted context omitted.

How long will this process take? Is it enough to create a new therapy to target the mutated cancer?

People develop resistance to TKIs (tyrosine kinase inhibitors, the previous mode of therapy) within months; you could keep chasing the dragon, but the tumor is just going to keep doing the same thing, shedding whatever mutation you target. In this case you're not even targeting mutations that the tumor relies on (as you are with a TKI), so there's absolutely no fitness cost to the tumor to evade.

Could you simultaneously target multiple mutations to reduce the risk of this? Similarly to using a cocktail of antibiotics to prevent the development of resistance.

i.e. the probability of shedding a single mutation is 1/x, but the probability of shedding two in the same organism is (1/x)^2, so targeting more mutations make it exponentially harder for the organism to adapt.

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#18

Post by jonknee »

astazangasta wrote: post #4

I'm calling it here, this trial will fail hard. The basic idea is this: the cancer has a number of mutations that produce novel antigens that don't exist in normal cells. If we can train T-cells to recognize these, they can attack the tumor with great specificity and kill those cells. The problem is, all the tumor has to do to evade this targeting is shed the problematic mutation, which is easily done - tumors are gr…

Almost all trials fail, but it's interesting that CRISPR is getting the nod. It has so many uses that if it doesn't work in this specific cancer study it doesn't really matter.

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#19

Post by dghughes »

unimpressive wrote: post #11
astazangasta wrote: post #9

Earlier quoted context omitted.

I do cancer research at UCSF on an immunotherapy project...

I'm not one to usually complain about downvotes, but this is ridiculous. The HN hivemind at its most absurd. This person is literally working in the research sector involved, giving their opinion (it's not a nice opinion, but it is presumably informed), and getting downvoted because the HN crowd doesn't like it. EDIT: At the time I wrote this comment the parent comment and the root comment were both far into the nega…

Well, we all know that now but not for the first comment.

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#20

Post by dnautics »

astazangasta wrote: post #7
return0 wrote: post #5

Earlier quoted context omitted.

How long will this process take? Is it enough to create a new therapy to target the mutated cancer?

People develop resistance to TKIs (tyrosine kinase inhibitors, the previous mode of therapy) within months; you could keep chasing the dragon, but the tumor is just going to keep doing the same thing, shedding whatever mutation you target. In this case you're not even targeting mutations that the tumor relies on (as you are with a TKI), so there's absolutely no fitness cost to the tumor to evade.

hey - just want clarification. I thought TKIs like gleevec give an asymptomatic period of years - do you mean by "develop resistance" the initial seed population of cells that are resistant emerge from a (presumably clonal or near-clonal) pool within months?

Second: Do you know if clinically, agents like gleevec are primarily used as standalone or in conjunction with more aggressive (and, unfortunately, side-effect laden) therapies? I was always a bit aware of the pernicious "maintenance drug" status of gleevec, but presumably if you combine it with an orthogonal therapy you could get higher coverage and better statistical odds of sending the patient into remission.

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