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> The hope is that, without PD-1, the edited cells will attack and defeat the cancer. It seems that we already have good drugs which inhibit interaction between PD-1 and PD-L1 is there really enough benefit from this?
Earlier quoted context omitted.
Luckily the article linked to the clinical trials.gov record for this trial [1] which suggests that the first approach (editing vs selection) is being used. 1. https://clinicaltrials.gov/ct2/show/NCT02793856?term=crispr&...
That seems to be the favorite interpretation. We need to see what data they present that favors it (ie % survival of the treated cells, number of initial cells, % mutants at that location detected in control cells). Also, this is kind of weird, because they say it is non-randomized: Study Design: Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Lab…
I suspect the randomization relates to the allocation to the experimental arms as described on the reporting page:
This is a dose-escalation study of ex-vivo knocked-out,
expanded, and selected PD-1 knockout-T cells from
autologous origin. Patients are assigned to 1 of 3
treatment groups to determine the maximal tolerant doseSo this title is a bit misleading; something like, "cells edited with CRISPR injected into a person for the first time" would be better. While CRISPR is promising for topological treatments, that's not what happened here. The team took white blood cells out of a patient's body, used CRISPR to knock out a gene which suppresses immune response, then injected those same cells back into the patient, hoping that they woul…
This study was in vitro (and then in vivo!)
I would agree, though, that most people would have thought "in vivo" from the title alone, since the prospect of and actual practicality of doing it in vivo is what really differentiates CRISPR from the tech that came before it.
> The hope is that, without PD-1, the edited cells will attack and defeat the cancer. It seems that we already have good drugs which inhibit interaction between PD-1 and PD-L1 is there really enough benefit from this?
Those drugs cost $100K+ per year, and have toxicity.
It will be interesting to see if there are differences in side effect profiles in the PD-1 knockout T-cells vs our current biologicals, however.
This makes me feel that i.e. looking for bone marrow donors may become obsolete in some cases, if we know the gene sequence responsible for the disease. Instead of looking for donors, it may actually be possible to repair bone marrow cells and inject them back, fixing the problem. Am I missing something here?
I think the best (or worst?) part is that CRISPR can be used with a 'gene drive' it keeps the changes active on on-going it's not a one shot thing. GATTACA?
Can't CRISPR achieve stable transfection through pathways like AAV, though? If that's the case, can't the cell lines carry on the changes without any need for on-going therapy?
Earlier quoted context omitted.
I don't think anyone is; it's still too far out there. I'm sure that there's plenty of research building towards it, but I couldn't name any names. I'm also an outsider to the industry, but CRISPR is actually a simple protocol that doesn't require much advanced equipment, and I've been looking into using it for some home science projects. The problem as I understand it is that right now, CRISPR requires some manual s…
Project idea: The death cap mushroom is really tasty according to people who are now dead. Disable the poison.
> The hope is that, without PD-1, the edited cells will attack and defeat the cancer. It seems that we already have good drugs which inhibit interaction between PD-1 and PD-L1 is there really enough benefit from this?
Those drugs cost $100K+ per year, and have toxicity.
Also, there is toxicity associated with gene modification. Take a look at the patient deaths with CAR-T therapy.
Earlier quoted context omitted.
Those drugs cost $100K+ per year, and have toxicity.
I can't imagine that personalized gene editing therapy will ever be cheaper than the current checkpoint blockade agents. It will be interesting to see if there are differences in side effect profiles in the PD-1 knockout T-cells vs our current biologicals, however.
Checkpoint blockade alone is a great development, but having treated patients with these drugs, I can tell you it is far from a cure for 80% of people.