As the recognition between natural killer (NK) cells and cancer cells does not require antigen presentation, NK cells are being actively studied for use in adoptive cell therapies in the rapidly evolving armamentarium of cancer immunotherapy. In addition to utilizing NK cells, recent studies have shown that exosomes derived from NK cells also exhibit antitumor properties. Furthermore, these NK cell‐derived exosomes exhibit higher stability, greater modification potentials and less immunogenicity compared to NK cells. Therefore, technologies that allow highly sensitive and specific isolation of NK cells and NK cell‐derived exosomes can enable personalized NK‐mediated cancer therapeutics in the future. Here, a novel microfluidic system to collect patient‐specific NK cells and on‐chip biogenesis of NK‐exosomes is proposed. In a small cohort of non‐small cell lung cancer (NSCLC) patients, both NK cells and circulating tumor cells (CTCs) were isolated, and it is found NSCLC patients have high numbers of NK and NK‐exosomes compared with healthy donors, and these concentrations show a trend of positive and negative correlations with bloodborne CTC numbers, respectively. It is further demonstrated that the NK‐exosomes harvested from NK‐graphene oxide chip exhibit cytotoxic effect on CTCs. This versatile system is expected to be used for patient‐specific NK‐based immunotherapies along with CTCs for potential prognostic/diagnostic applications.
Natural killer (NK) cell functionality is a strong indicator of favorable prognosis in cancer patients, making NK cells an appealing therapeutic target to prevent lymph node dissemination. We engineered liposomes that are conjugated with anti‐CD335 antibodies for NK cell targeting, and the apoptotic ligand TRAIL to kill cancer cells. Liposomes were made using a thin film hydration method followed by extrusion to approximately 100 nm in diameter and conjugation of proteins via thiol‐maleimide click chemistry. TRAIL/anti‐CD335 liposomes successfully bound to isolated NK cells. Once piggybacked to the surface of NK cells, these “Super Natural Killer Cells” were able to more effectively kill oxaliplatin‐resistant SW620 cells and metastatic COLO205 colorectal cancer cells via TRAIL‐mediated apoptosis compared to NK cells alone. Importantly, Super NK cells were more effective under physiological levels of fluid shear stress found in the lymphatics. Liposome biodistribution after intravenous administration confirmed the sustained presence of liposomes within the spleen and tumor draining mesenteric lymph nodes for at least 4 days. These results demonstrate the enhanced apoptotic effects of NK cells armored with liposomal TRAIL against clinically relevant colorectal cancer cells, providing the groundwork for in vivo treatment studies in mouse models of colorectal cancer metastasis.
more » « less- NSF-PAR ID:
- 10472828
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Biomedical Materials Research Part A
- Volume:
- 112
- Issue:
- 1
- ISSN:
- 1549-3296
- Format(s):
- Medium: X Size: p. 110-120
- Size(s):
- ["p. 110-120"]
- Sponsoring Org:
- National Science Foundation
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