Great podcast on engineering B cells to produce specific antibodies- was just thinking about this problem the other dayhttps://twitter.com/profvrr/status/1156546386529267714?s=21 …
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Adam Strandberg Retweeted Vincent Racaniello
Great podcast on engineering B cells to produce specific antibodies- was just thinking about this problem the other dayhttps://twitter.com/profvrr/status/1156546386529267714?s=21 …
Adam Strandberg added,
Typically we use vaccines to protect against pathogens- they imitate a real infection sufficiently well to convince the immune system to generate B cells that produce antibodies against the pathogen
But this can be difficult for many reasons- many viruses such as Respiratory Syncytial Virus have no vaccine. This is bad particularly for immunocompromised patients, like those who have just had organ transplants
What if instead we just identified a gene coding for an antibody that works, and directly modified your B cells to do that?
This turns out to be feasible using CRISPR/Cas9. You can insert a gene coding for a specific antibody region in a location that silences expression of whatever antibody the B cell previously coded for
The location is also relatively constant across people (contains no SNPs with >1% prevalence), so it’s a good target
There are some difficulties though, not the least of which is somatic hypermutation- B cells introduce random mutations to the genes encoding antibodies (in order to have the diversity the adaptive immune system is famous for)-means the engineered cells could become self-reactive
Research into suppressing somatic hypermutation in these cells would be super useful imo, interesting to see whether you could do it with another CRISPR knockout
Then of course there are the infamous off-target mutations in CRISPR systems. There seems to be a legion of people working on that so if it’s possible to fix I’m confident it will be
And finally cost- CAR-T is a similar therapeutic strategy involving custom-modifying T cells from the patient and costs about $100k
Presumably this can be brought way down if scaled up? unless someone gets in the way of that
yeah have either of you come across estimates on the actual variable cost for these procedures? (I assume the price is mostly amortized drug portfolio r&d)
CAR-T is very new so it is a combo amortized R&D and leveraging willingness-to-pay with principal-agent problems. Misremembered the price though, it's $500k for the drug with >$500k in expected associated costshttps://www.healio.com/hematology-oncology/cell-therapy/news/online/%7B124396e7-1b60-4cff-a404-0a2baeaf1413%7D/car-t-cell-therapy-total-cost-can-exceed-15-million-per-treatment …
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