Nkarta Inc (NKTX)

[jondoeuk]

MICA and MICB, as well as ULBP 1-6 expression is tightly restricted in healthy cells, only upregulated during stress and cellular transformation [1], and are recognised by the NKG2D receptor, which activates NK cells [2]. However, looking at just AML, expression can vary [3,4].

So going forward, I hope to see a number of different combinations tested. Bortezomib can increase the cell surface expression of NKG2D ligands, resulting in the increased killing by NK cells [5]. Histone deacetylase inhibitors have also been shown to increase expression of NKG2D ligands [6-8]. Treatment resulted in increased recognition and increased sensitivity to NK cell lysis [9]. In addition, all-trans retinoic acid or valproic acid in patients with AML induced NKG2D ligands on the surface of leukemic cells [10,11].

Finally, the use of a PARP1 inhibitor, could increase AML leukemic stem cell killing [12].

Refs:
1 https://www.annualreviews.org/doi/full/10.1146/annurev-immunol-032712-095951
2 https://www.science.org/doi/10.1126/science.285.5428.727
3 https://www.jimmunol.org/content/189/3/1360.long
4 https://ashpublications.org/blood/article/105/9/3615/21291/Ligands-for-natural-killer-cell-activating
5 https://aacrjournals.org/cancerres/article/68/5/1546/542412/Selective-Induction-of-Expression-of-a-Ligand-for
6 https://aacrjournals.org/cancerres/article/65/23/11136/518911/Cancer-Cells-Become-Susceptible-to-Natural-Killer
7 https://aacrjournals.org/cancerres/article/65/14/6321/518359/Natural-Killer-Cell-Mediated-Lysis-of-Hepatoma
8 https://www.pnas.org/doi/abs/10.1073/pnas.1008522107
9 https://clinicalsarcomaresearch.biomedcentral.com/articles/10.1186/2045-3329-2-8
10 https://www.sciencedirect.com/science/article/pii/S0006497120482278
11 https://www.frontiersin.org/articles/10.3389/fimmu.2020.580328/full
12 https://cancerdiscovery.aacrjournals.org/content/9/9/OF13