Cancer immunotherapies utilize the capabilities of the immune system to efficiently target
malignant cells. In recent years, chimeric antigen receptor (CAR) equipped T cells showed
promising results against B cell lymphomas. Autologous CAR-T cells require patientspecific
manufacturing and thus extensive production facilities, resulting in high priced
therapies. Along with potentially severe side effects, these are the major drawbacks of
CAR-T cells therapies. Natural Killer (NK) cells pose an alternative for CAR equipped
immune cells. Since NK cells can be safely transferred from healthy donors to cancer
patients, they present a suitable platform for an allogeneic “off-the-shelf” immunotherapy.
However, administration of activated NK cells in cancer therapy has until now shown poor
anti-cancer responses, especially in solid tumors. Genetic modifications such as CARs
promise to enhance recognition of tumor cells, thereby increasing anti-tumor effects and
improving clinical efficacy. Although the cell biology of T and NK cells deviates in many
aspects, the development of CAR-NK cells frequently follows within the footsteps of CART
cells, meaning that T cell technologies are simply adopted to NK cells. In this review, we
underline the unique properties of NK cells and their potential in CAR therapies. First, we
summarize the characteristics of NK cell biology with a focus on signaling, a fine-tuned
interaction of activating and inhibitory receptors. We then discuss why tailored NK cellspecific
CAR designs promise superior efficacy compared to designs developed for T
cells. We summarize current findings and developments in the CAR-NK landscape:
different CAR formats and modifications to optimize signaling, to target a broader pool of
antigens or to increase in vivo persistence. Finally, we address challenges beyond NK cell
engineering, including expansion and manufacturing, that need to be addressed to pave
the way for CAR-NK therapies from the bench to the clinics.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:85870 |
| Date | 08 June 2023 |
| Creators | Ruppel, Katharina Eva, Fricke, Stephan, Köhl, Ulrike, Schmiedel, Dominik |
| Publisher | Frontiers Media S.A. |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 822298 |
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