Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan-Dec;15(1):2208697.
doi: 10.1080/19420862.2023.2208697.

Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors

Kerry A Whalen  1 , Kavya Rakhra  1 , Naveen K Mehta  1 , Alexander Steinle  2   3 , Jennifer S Michaelson  1 , Patrick A Baeuerle  1   4
Affiliations
Review

Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors

Kerry A Whalen et al. MAbs. 2023 Jan-Dec.

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).

Keywords: ADCC; CD16A; MICA; MICB; NK cell; NKG2D; monoclonal antibody.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Depicted from left to right are: NK cell, cancer cell and CD 8+ T cell. Receptors and corresponding ligands are displayed on the cells and depicted as icons.
Figure 1.
Select activating and inhibitory receptors on NK cells and CD8 T cells and their corresponding ligands.
Color-coded heat map that represents the intensity of NKG2D ligand expression in cancer tissues.
Figure 2.
Broad expression of MICA and MICB in human cancers.
A 3D structure of MICA protein on a stressed cell is depicted bound to NKG2D represented as a 3D structure on an NK cell.
Figure 3.
Structure of the NKG2D-MICA complex. .
An illustration using icons to represent protein, cell-based and vaccine therapeutics that target cancer cells expressing NKG2D ligands.
Figure 4.
Schematic representation of therapeutic modalities targeting the MICA/B pathway.
See this image and copyright information in PMC

References

    1. Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, et al. Use of CAR-Transduced natural killer cells in CD19-positive lymphoid tumors. N Engl J Med. 2020;382(6):545–15. PMID: 32023374. doi:10.1056/NEJMoa1910607. - DOI - PMC - PubMed
    1. Mensali N, Dillard P, Hebeisen M, Lorenz S, Theodossiou T, Myhre MR, Fane A, Gaudernack G, Kvalheim G, Myklebust JH, et al. NK cells specifically TCR-dressed to kill cancer cells. EBioMedicine. 2019;40:106–17. PMID: 30665853. doi:10.1016/j.ebiom.2019.01.031. - DOI - PMC - PubMed
    1. Morton LT, Wachsmann TLA, Meeuwsen MH, Wouters AK, Remst DFG, van Loenen MM, Falkenburg JHF, Heemskerk MHM, van Loenen MM.. T cell receptor engineering of primary NK cells to therapeutically target tumors and tumor immune evasion. J ImmunoTher Cancer. 2022;10(3):e003715. PMID: 35288464. doi:10.1136/jitc-2021-003715. - DOI - PMC - PubMed
    1. Xie G, Dong H, Liang Y, Ham JD, Rizwan R, Chen J. CAR-NK cells: a promising cellular immunotherapy for cancer. EBioMedicine. 2020;59:102975. doi:10.1016/j.ebiom.2020.102975. PMID: 32853984. - DOI - PMC - PubMed
    1. Marofi F, Abdul-Rasheed OF, Rahman HS, Budi HS, Jalil AT, Yumashev AV, Hassanzadeh A, Yazdanifar M, Motavalli R, Chartrand MS, et al. CAR-NK cell in cancer immunotherapy; a promising frontier. Cancer Sci. 2021;112(9):3427–36. PMID: 34050690. doi:10.1111/cas.14993. - DOI - PMC - PubMed

Substances