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Unnatural killer cells to prevent bloodborne metastasis: inspiration from biology and engineering
Michael J Mitchell1, Michael R King
1Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Abstract:
Metastasis contributes to over 90% of cancer-related deaths. Many types of cancer metastasize via the bloodstream, where circulating tumor cells (CTCs) originating from the primary tumor can undergo selectin-mediated adhesion with the blood vessel wall and subsequently transmigrate to anatomically distant organs. In an effort to neutralize CTCs with the potential to form metastases, a new therapeutic approach has been developed in which circulating leukocytes are functionalized to target and kill cancer cells in the bloodstream. This approach mimics the cytotoxic activity of natural killer cells and the chemical engineering concept of a fluidized bed reactor, which increases the surface area for surface-catalyzed reactions. The resulting 'unnatural killer cells', proven effective in vitro with human blood and also in the living mouse, holds promise in neutralizing CTCs to interrupt the metastasis process.
Insights
A novel therapeutic strategy functionalizes leukocytes to create "unnatural killer cells" that target and eliminate circulating tumor cells (CTCs) in the bloodstream, potentially preventing cancer metastasis.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Immunotherapy
Background:
- Metastasis, the spread of cancer cells, is responsible for over 90% of cancer deaths.
- Circulating tumor cells (CTCs) travel via the bloodstream, adhering to blood vessel walls and migrating to distant organs.
- Current treatments often struggle to effectively target and eliminate these disseminated tumor cells.
Discussion:
- A new approach engineers circulating leukocytes to function as cytotoxic agents against CTCs.
- This strategy leverages principles from natural killer cell activity and fluidized bed reactors for enhanced efficacy.
- The engineered cells, termed 'unnatural killer cells', demonstrate effectiveness in vitro and in vivo.
Key Insights:
- Functionalized leukocytes can be engineered to specifically target and destroy CTCs within the bloodstream.
- The 'unnatural killer cell' concept offers a potential method to intercept cancer spread at an early stage.
- This approach shows promise in preclinical models, suggesting a new avenue for anti-metastasis therapy.
Outlook:
- Further research and clinical trials are needed to validate the safety and efficacy of unnatural killer cells in human patients.
- This innovative strategy could lead to novel treatments aimed at preventing metastasis and improving cancer patient outcomes.
- The development represents a significant advancement in the field of targeted cancer therapy and immunotherapy.
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