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Crispr Wins Key Approval to Fight Cancer in Human Trials

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

#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 great at acquiring novel mutations to become resistance to therapy, losing a mutation is even easier. All you have to do is ditch one arm of a chromosome, revert the mutation, or otherwise eliminate the novel mutation, and your tumor cell is now resistant to this therapy.

Add to this the fact that we are basically shit at predicting which mutant proteins will produce neoantigens and you have a recipe for total failure, even in concept.

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

#5

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…

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

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

#6

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…

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...

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

#7
post #5

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…

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.

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

#8

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…

"Add to this the fact that we are basically shit at predicting which mutant proteins will produce neoantigens and you have a recipe for total failure, even in concept."

Do you think if we had more data surrounding those mutant proteins we could start predicting better?

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

#9
post #6

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…

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...
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