15353-j-veluchamy

4 NK cell ADCC enhances treatment efficacy in colorectal cancer | 99 cetuximab, cytotoxicity assays were performed with NK cells from 6 donors, 3 with the V/V polymorphism and 3 with the V/F polymorphism. Cytotoxicity against A431 and degranulation of the CD16 + NK cell fraction was assessed after a 4hr co-culture of cetuximab coated A431 cells and NK cells. No significant differences in target cell death (Figure 3A) or degranulation (Figure 3B) were observed between NK cell donors with V/V and V/F CD16/ FcγRIIIa polymorphism. NK cells efficiently lyse EGFR + / - and RAS wt / mut colon cancer cell lines Having established the anti-tumor efficacy of the cetuximab/NK cell combination with the EGFR +++ cell line A431, our next aim was to extend these findings to colon cancer cell lines COLO320 (EGFR - , RAS wt ), SW480 (EGFR + RAS mut ; KRAS exon 2 c.35>T; p.G12V), SW620 (EGFR + Figure 1: Cetuximab and panitumumab binding affinities and their cytotoxicity towards EGFR +++ tumor targets EGFR overexpressing A431 cells were used to test anti-EGFR mAbs. A and B, Histograms showing binding of 100μg/ml of biotinylated cetuximab (A) and panitumumab (B) to A431 cells. Grey shades represents the streptavidin APC control, black shades represent binding of the biotinylated mAbs. (C) Dose response curve to measure EC 50 concentration for cetuximab and panitumumab. A431 cells treated with cetuximab and panitumumab at concentrations of 1ng, 1µg, 5µg, 10µg, 100µg and 1000µg per ml for 4 hrs were analyzed for target cell death.

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