Nkarta Inc (NKTX)

[jondoeuk]

I assume (rightly or wrongly) that expression of HLA class I and II will be disrupted through genetic ablation of beta 2 microglobulin (B2M) and the class II transactivator (CIITA), respectively, allowing evasion of the patient's adaptive immune system, with the CD38 gene also being ablated as well.

If so, CD38-targeted mAbs, such as daratumumab, are approved for the treatment of multiple myeloma. CD38 has also been shown to be highly expressed on activated immune cells, including CD8+ T-cells, CD4+ T-cells, and NK cells. FATE has incorporated the knock-out of CD38 into some of its iPSC-derived products, which uniquely allows for CD38-null, iPSC-derived cells to be combined with CD38-targeted mAbs and avoid fratricide. In one ASH presentation [1], scientists from the company showed that the administration of daratumumab selectively depleted allogeneic CD38+ NK and T-cells and uniquely enabled CD38-null iNK cells to functionally persist through Day 28 compared to non-edited iNK cells. These preclinical data were supported by translational findings from the PhI trial of FT576, its multiplexed-engineered, BCMA-targeted CAR-NK cell product candidate that incorporates the knock-out of CD38, where combination with daratumumab rapidly and selectively eliminated CD38+ patient immune cells through the first month of therapy. The translational findings suggest that following administration of daratumumab, CD38-null iNK cells may avoid rejection by activated host immune cells without requiring conditioning chemotherapy.

Ref:
1 https://ashpublications.org/blood/article/140/Supplement%201/7388/492103/iPSC-Derived-CD38-Null-NK-Cells-in-Combination