Precision BioSciences Inc (DTIL)

[jondoeuk]

Thanks for posting, JonDoe. Although this looks like an exciting potential enhancement, it seems pretty far off at this point. My guess is that there is still animal work to be done before trying tuis in humans. Do you gave any idea of the stage in development at thus point?

It is preclinical.

It is quite exciting to see how engineering can be employed with the ability to genetically modify in or out.

In addition to shRNA knockdown for that (deoxycytidine kinase), the patent also covers CD319, TGFRB2, CBL-B, CD52 and the glucocorticoid receptor.

Add these kinds of improvements to the stealth advancements and sprinkle in multiple antigens and CAR-Ts are here to stsy.

You can start from the ground up. By that I mean select donors for T-cell phenotypes that correlate with complete responses. In R/R CLL it was CD8+CD27+PD-1- [1], while R/R LBCL, CD8+CCR7+CD27+ [2]. How you expand, with more than just cytokines [3,4]. The design of the CAR [5,6]. An additional signaling domain to improve in vivo expansion and/or persistence [7], as well as scFv-optimisation for targeting [8]. Also, remove exhausted and senescent cells, both before and after manufacturing.

This, with the stealth cells and shRNA knockout (hopefully, to other genes) that could be 'personalised,' would increase the depth and duration of responses across a broad range of types, including solid tumours.

You know I love the dendritic cell vaccine technology, but the two don’t have to be mutually exclusive.

Well, vaccines (DC, synthetic peptide, viral vector, and others) don't really show much, if any activity in patients with advanced/metastatic disease. The use of adoptive cell transfer does, with some patients being cured.

Cancer treatments are about to take a giant leap into the future and CAR-Ts have only just gotten started.

Agreed.

Refs:
1 https://www.nature.com/articles/s41591-018-0010-1
2 https://www.nature.com/articles/s41591-020-1061-7
3 https://www.nature.com/articles/s41467-020-20696-x
4 https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0804-9
5 https://www.biorxiv.org/content/10.1101/2021.07.11.451980v1.full
6 https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00658-9
7 https://www.nature.com/articles/nm.4478
8 https://www.nature.com/articles/s42003-021-01791-1