PhD Student Florida A&M University Tallahassee, Florida
This study evaluated natural killer cell-derived EVs (NK-EVs) as anticancer agents for resistant H1975 lung cancer. NK-EVs isolated by ultracentrifugation were characterized by NTA, AFM and western blotting (which showed the presence of cytotoxic proteins perforin and granzyme). Cytotoxicity studies using 2D and 3D osimertinib resistant H1975 lung cancer cells (with EGFR-L858R mutation) demonstrated that NK-EVs effected cell viability (P < 0.001) and in-vivo tumor xenograft model studies showed that tumor volumes for NK-EVs, carboplatin and NK-EVs + carboplatin groups were 84%, 65%, 30% (P < 0.001) as compared to the control group respectively. Western blotting revealed that NK-EVs downregulated PD-1/PD-L1 axis along with SOD2, PARP, NF-kB, TGF-ß and SET (P < 0.001). Proteomics and RNA sequencing of NK-EVs disclosed the cytotoxic proteins and miRNAs (miR-1-3P/149-5P/320a/186-5p/339-5p) respectively. Further, miRNAs known for tumor suppression were picked out for further investigations like flow cytometry, fluorescent staining studies and PCR etc. to understand the molecular mechanisms.
Learning Objectives:
Upon completion, participants will be able to isolate, characterize and use natural killer (NK) cell-derived extracellular vesicles for the treatment of resistant lung cancer and explore other immune cell EVs.
Upon completion, participants will be able to use natural killer (NK) cell-derived extracellular vesicles for delivering drugs and therapeutic miRNAs which regulate PD-L1 for the treatment of resistant lung cancer.
Upon completion, participants will be able to conduct experiments for in-vitro and in-vivo studies to understand the potential benefits of the NK-EVs in treating resistant lung cancer.