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ABSTRACT
The field of immuno-oncology has revolutionized cancer patient care and improved survival and quality of life for patients. Much of the focus in the field has been on exploiting the power of the adaptive immune response through therapeutic targeting of T cells. While these approaches have markedly advanced the field, some challenges remain, and the clinical benefit of T cell therapies does not extend to all patients or tumor indications. Alternative strategies, such as engaging the innate immune system, have become an intense area of focus in the field. In particular, the engagement of natural killer (NK) cells as potent effectors of the innate immune response has emerged as a promising modality in immunotherapy. Here, we review therapeutic approaches for selective engagement of NK cells for cancer therapy, with a particular focus on targeting the key activating receptors NK Group 2D (NKG2D) and cluster of differentiation 16A (CD16A).
Acknowledgments
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Disclosure statement
No potential conflict of interest was reported by the author(s).
Abbreviations
| AA | = | Amino acid |
| ADAM10 | = | a disintegrin and metalloproteinase-10 |
| ADAM17 | = | a disintegrin and metalloproteinase-17 |
| ADCC | = | Antibody-dependent cellular cytotoxicity |
| ADCP | = | antibody-dependent cellular phagocytosis |
| ADC(s) | = | antibody-drug conjugates |
| aKIR(s) | = | activating killer Ig-like receptors |
| AML | = | acute myeloid leukemia |
| ANKET | = | Antibody-based NK cell Engager Therapeutics |
| B7H3 | = | B7 homolog 3 protein |
| BCMA | = | B-cell maturation antigen |
| CAR | = | Chimeric antigen receptor |
| CCR4 | = | C-C chemokine receptor type 4 |
| CD | = | Cluster of differentiation |
| CD16A | = | Cluster of differentiation 16A |
| CD3ζ | = | CD3 zeta |
| CD96 | = | cluster of differentiation 96 |
| CDC | = | complement-dependent cytotoxicity |
| CRS | = | Cytokine release syndrome |
| DAP10 | = | DNAX-activating protein 10 |
| DNAM-1 | = | DNAX accessory molecule-1 |
| ECD | = | extracellular domain |
| ERP5 | = | endoplasmic reticulum protein 5 |
| Fab | = | fragment antigen-binding |
| FcϵRIγ | = | Fc epsilon RI |
| Fcγ1 | = | Fc gamma domain 1 |
| FcγRIIIa | = | Fc-gamma receptor IIIA |
| FcγRs | = | Fc gamma receptors |
| FUT8 | = | fucosyltransferase |
| GMD | = | GDP mannose 4,6-dehydratase |
| GPI | = | glycosylphosphatidylinositol |
| Grb | = | growth factor receptor bound 2 protein |
| HCC | = | hepatocellular carcinoma |
| HER2 | = | human epidermal growth factor receptor 2 |
| HL | = | Hodgkin lymphoma |
| HLA | = | human leukocyte antigen |
| ICANs | = | Immune effector cell-associated neurotoxicity syndrome |
| iKIR(s) | = | inhibitory killer Ig-like receptors |
| IL-15 | = | interleukin-15 |
| IL-2 v | = | interleukin-2 variant |
| Ipsc | = | induced pluripotent stem cell |
| IRp60 | = | inhibitor receptor protein |
| ITAM | = | immunoreceptor tyrosine-based activation motif |
| KIR2DL1-L3 | = | killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1–3 |
| KIR3DL2 | = | killer cell immunoglobulin like receptor three Ig domains and long cytoplasmic tail 2 |
| LAIR-1 | = | leukocyte-associated immunoglobulin-like receptor 1 |
| mAb | = | monoclonal antibody |
| MDS | = | myeloid dysplastic syndrome |
| MHC | = | Major histocompatibility complexes |
| MICA | = | MHC class I chain-related protein A |
| MICB | = | MHC class I chain-related protein sequence B |
| MICA/B | = | MICA and MICB |
| MM | = | Multiple myeloma |
| MMP-9 | = | matrix metalloproteinase-9 |
| MMP-14 | = | matrix metalloproteinase −14 |
| NCR | = | natural cytotoxicity receptors |
| NFAT | = | nuclear factor of activated T-cells |
| NFKB | = | nuclear factor kappa-light-chain-enhancer of activated B cells |
| NK | = | Natural Killer |
| NKCEs | = | NK cell engagers |
| NKG2A | = | Natural Killer Group 2A |
| NKG2C | = | Natural Killer group 2C |
| NKG2D | = | Natural Killer Group 2D |
| NKT | = | Natural Killer T cell |
| PBD | = | pyrrolobenzodiazepine dimers |
| PD-1 | = | programmed cell death 1 receptor |
| PD-L1 and PD-L2 | = | programmed death-ligand 1 and 2 |
| PI3K | = | phosphoinositide 3-kinase |
| scFv | = | single-chain variable fragment |
| siglec-7 | = | sialic acid binding Ig like lectin 7 |
| sMICA/B | = | soluble MICA/B |
| Tandab | = | tandem diabody |
| TCGA | = | The Cancer Genome Atlas |
| TCR | = | T cell receptor complex |
| TIGIT | = | T cell immunoreceptor with Ig and ITIM domains |
| TIM-3 | = | T cell immunoglobulin and mucin domain-containing protein 3 |
| TME | = | tumor microenvironment |
| TriNKET | = | Tri-specific NKCE |
| ULBPs | = | UL-16- binding proteins |
| VEGFR2 | = | vascular endothelial growth factor receptor 2. |