PhD Student Florida A&M University Tallahassee, Florida
We investigated the potential of miRNA-loaded NK-EVs (targeting PD-L1/FOXM1) in combination with Carboplatin against Osimertinib-resistant PDX and H1975R lung cancer cells (bearing EGFR mutations L858R and TM00199) in-vitro and in-vivo. Briefly, 3D Cytotoxicity assays showed that NK-EVs induced cytotoxicity against both cell lines and reduced Carboplatin’s IC50 by ⁓1.9-fold and ⁓1.7-fold in PDX and H1975R cells, respectively. In both the cells, miR-5193 and miR-149-5p showed 44-48% and 38-40% cell death at 50 nM (p < 0.001). MiR-5193/149-5p-NK-EVs showed enhanced cytotoxic effects (P < 0.01). PDX xenograft model resulted in significant reduction (P < 0.001) in tumor volume (TV). Although the miR-5193/149-5p-NK-EVs themselves showed reduced TV by ⁓1.5-fold, miR-5193/149-5p-NK-EVs+Carboplatin groups reduced TV by ⁓3-fold (p < 0.001). PD-1/PD-L1 were downregulated along with FOXM1, Phospho-STAT3, NF-kB-p65, CD1, CDK6 and IL-1ß indicating apoptosis, cell growth inhibition and anti-inflammatory activity (p < 0.001 vs control). In H1975R xenografts, miR-5193-149-5p-NK-EVs combination group showed ⁓3-fold reduction in TV and ⁓4-fold when combined with Carboplatin (p < 0.001).
Learning Objectives:
Upon completion, participants will be able to use natural killer (NK) cell-derived extracellular vesicles for delivering therapeutic miRNAs which regulate PD-L1 and FOXMI for the treatment of resistant lung cancer
Participants will be able to understand therapeutic miRNA loading and characterization of loaded NK-EVs.
Participants will be able to use NK-EVs and perform in vitro and in vivo experiments to see the outcome in cancer therapy.
