Increased Susceptibility of the CD57 - NK Cells Expressing KIR2DL2/3 and NKG2C to iCasp9 Gene Retroviral Transduction and the Relationships with Proliferative Potential, Activation Degree, and Death Induction Response

• Published in: International journal of molecular sciences Vol. 22; no. 24; p. 13326
• Main Authors: Palamarchuk, Anastasia I, Alekseeva, Nadezhda A, Streltsova, Maria A, Ustiuzhanina, Maria O, Kobyzeva, Polina A, Kust, Sofya A, Grechikhina, Maria V, Boyko, Anna A, Shustova, Olga A, Sapozhnikov, Alexander M, Kovalenko, Elena I
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11-12-2021; MDPI
• Subjects: adoptive NK cells; Apoptosis; Cancer; Cancer immunotherapy; CD57 antigen; Cell Death; Cell Proliferation; CRISPR-Cas Systems; Cytotoxicity; Dimerization; Efficiency; Gene Expression Regulation; Genetic modification; genetic modifications; Genetic Vectors; Graft versus host disease; Histocompatibility antigen HLA; HLA-DR; Humans; Immunotherapy; Insertion; K562 Cells; Killer Cells, Natural; Lymphocyte Activation; Lymphocytes; Natural killer cells; NK Cell Lectin-Like Receptor Subfamily C - biosynthesis; NK Cell Lectin-Like Receptor Subfamily C - genetics; NK cells; NKG2 antigen; Pathogens; Potassium channels (inwardly-rectifying); proliferation; Receptors, KIR2DL2 - biosynthesis; Receptors, KIR2DL2 - genetics; Receptors, KIR2DL3 - biosynthesis; Receptors, KIR2DL3 - genetics; retroviral vectors; Retroviridae; Suicide genes; Transduction; Transduction, Genetic; genetic modifications; suicide switch; NK cells; HLA-DR; proliferation; transduction; adoptive NK cells; retroviral vectors; iCasp9 gene
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222413326

Nowadays, the use of genetically modified NK cells is a promising strategy for cancer immunotherapy. The additional insertion of genes capable of inducing cell suicide allows for the timely elimination of the modified NK cells. Different subsets of the heterogenic NK cell population may differ in proliferative potential, in susceptibility to genetic viral transduction, and to the subsequent induction of cell death. The CD57
NKG2C
NK cells are of special interest as potential candidates for therapeutic usage due to their high proliferative potential and certain features of adaptive NK cells. In this study, CD57
NK cell subsets differing in KIR2DL2/3 and NKG2C expression were transduced with the iCasp9 suicide gene. The highest transduction efficacy was observed in the KIR2DL2/3
NKG2C
NK cell subset, which demonstrated an increased proliferative potential with prolonged cultivation. The increased transduction efficiency of the cell cultures was associated with the higher expression level of the HLA-DR activation marker. Among the iCasp9-transduced subsets, KIR2DL2/3
cells had the weakest response to the apoptosis induction by the chemical inductor of dimerization (CID). Thus, KIR2DL2/3
NKG2C
NK cells showed an increased susceptibility to the iCasp9 retroviral transduction, which was associated with higher proliferative potential and activation status. However, the complete elimination of these cells with CID is impeded.