Looking at #iPSC Part 4
Here I want to look at some of the origins of the edits and some new ones. I also want to look at some of the edits goin on in other CAR-T programs that could make a difference in this space.
Here I want to look at some of the origins of the edits and some new ones. I also want to look at some of the edits goin on in other CAR-T programs that could make a difference in this space.
1/ $FATE was the first company to start working on iPSC. Its actually one of my oldest holdings as I owned it when iPSC was only an idea. They built a lot of technology on developing iPSC manufacturing. They can do thousands of doses per batch run for less than $2k per dose.
2/ They pioneered the IL15 cytokine stimulation in NK cells and the addition of an enhanced CD16 receptor that improved efficacy with antibodies. They even pioneered the concept of knocking out MHC I and MHC II and the insertion of HLA-E.
3/ When I say pioneered, I do mean them and the many academic organizations they worked with that did most of the research into these concepts. None of the alloevasion edits made it into any of the early Fate therapies.
4/ They pioneered FT516 which was their first basic progenitor cell with IL15 and enhanced CD16. They took this into other therapies like CD19 and BCMA for blood cancers.
5/ They even worked on doing CD38 knockout so these therapies can work with CD38 antibodies without killing the NK cells. One of their newest edits is very interesting. They developed an Alloimmune Defense Receptor (ADR).
6/ This receptor will kill any immune cells that bind to the NK cells and attempt to kill it. This is very interesting as only about 5% of T cells are reactive and contribute to rejection.
7/ If T cells have a response to kill these reactive engineered ADR cells, they would be killed instead. We will have to see more data on this technology as it could be an alternative to Hypoimmune or Alloevasion.
8/ The next program worth mentioning is being used in allogenic programs by $CRBU. They are using their CAR-T programs as a test bed for different edits. The first is the knockout of PD-1 in CAR-T. The other is doing MHC I and MHC II knockout and HLA-E insertion.
9/ They are also working on an iPSC program for NK cells. I think that will bring together all their learnings from the edits they develop using CAR-T. They seem to be the only CRISPR company that understands the importance of iPSC manufacturing.
10/ The last edits I want to mention are from $CRSP with their Regenase 1 and TGFBR2 knockouts. When I first heard about these, I was skeptical. I looked over the papers for these edits and their roles in the cell therapy tumor environment.
11/ Its very early data for these 2 edits, but I will be watching them as the data unfolds. Regenase 1 is a fitness edit. This is associated with cell exhaustion and durability.
12/ The TGFBR2 is associated with blocking T reg cells. This is because TGF is a key cytokine in the creation of T regulatory cells in the tumor environment.
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