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Natural Killer Cell-Based Cancer Immunotherapies: From Immune Evasion to Promising Targeted Cellular Therapies
1Department of Vascular Biology, Medical University of Vienna, Vienna, Austria.
Abstract:
Immunotherapies based on natural killer (NK) cells are among the most promising therapies under development for the treatment of so far incurable forms of leukemia and other types of cancer. The importance of NK cells for the control of viral infections and cancer is supported among others by the findings that viruses and tumors use a multitude of mechanisms to subvert and evade the NK cell system. Infections and malignant diseases can further lead to the shaping of NK cell populations with altered reactivity. Counter measures of potential therapeutic impact include the blocking of inhibitory interactions between NK cell receptors and their cellular ligands, the enhancement of activating receptor signals, and the infusion of large numbers of ex vivo generated and selected NK cells. Moreover, the specific cross-linking of NK cells to their target cells using chimeric antigen receptors or therapeutic bi-/trispecific antibody reagents is a promising approach. In this context, NK cells stand out by their positive effects and safety demonstrated in most clinical trials so far. Based in part on results of the recent EC-sponsored project "NATURIMMUN" and considering additional published work in the field, we discuss below new developments and future directions that have the potential to further advance and establish NK cell-based therapies at the clinics on a broader scale.
Insights
Natural killer (NK) cell immunotherapies show promise for treating leukemia and cancer. Strategies to enhance NK cell activity and direct them to targets are advancing clinical applications.
Area of Science:
- Immunology
- Oncology
- Cellular Therapy
Background:
- Natural killer (NK) cells are crucial for controlling viral infections and cancer.
- Tumors and viruses employ mechanisms to evade NK cell surveillance, altering NK cell function.
- NK cell-based immunotherapies are emerging as promising treatments for various cancers.
Purpose of the Study:
- To review new developments and future directions in NK cell-based immunotherapies.
- To discuss strategies for overcoming NK cell evasion by tumors and viruses.
- To highlight the potential for broader clinical application of NK cell therapies.
Main Methods:
- Blocking inhibitory NK cell receptor-ligand interactions.
- Enhancing activating NK cell receptor signals.
- Infusing ex vivo expanded and selected NK cells.
- Utilizing chimeric antigen receptors and bispecific/trispecific antibodies for NK cell targeting.
Main Results:
- NK cell therapies have demonstrated positive effects and safety in clinical trials.
- Various strategies are being developed to enhance NK cell anti-cancer activity.
- Targeted approaches like CARs and bispecific antibodies show promise for directing NK cells.
Conclusions:
- NK cell immunotherapies represent a significant advancement in cancer treatment.
- Further research and development are expected to broaden the clinical use of NK cell therapies.
- Optimizing NK cell function and targeting strategies will be key to their success.
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