15353-j-veluchamy

5 Towards UCB-NK cells treatment in colorectal cancer | 127 35 after tumor inoculation. Figure 4A depicts four representative BLI images from each group at day 35 post-tumor injection and average radiance from range of interest (ROI) measurements are shown in Figure 4B. It is clear that mice from groups A and B showed a higher and more diffuse tumor load compared to mice treated with UCB-NK alone or in combination with cetuximab. In order to demonstrate the possibility of antitumor efficacy of cetuximab in the BRGS mouse model we performed a similar tumor challenge using the cetuximab sensitive A431 cell line, which bears wild-type RAS and overexpresses EGFR. A significant decrease in tumor load was observed when A431 tumors were treated with the same concentration of cetuximab as in the SW480 study (Figure 4C), confirming the in vivo functionality of cetuximab. We next assessed whether treatment of SW480 bearing mice with UCB-NK cells alone or in combination with cetuximab translated into a survival advantage (Figure 5). Indeed, treatment of mice with UCB-NK cells alone resulted in a significant prolongation in their life span (p=0.01), whereas combinatorial therapy did not add significantly to this. Treatment with cetuximab alone did not translate into a significant survival advantage, consistent with the observed effects on tumor growth. Figure 5: Significant survival benefit in cetuximab resistant RAS mutant tumor bearing mice treated with UCB-NK cells Kaplan -Meier survival curves were plotted for the total experimental study period from day 0 until day 65. Survival rates of SW480 (EGFR + , RAS mut ) tumor bearing mice (n=6 per group) following treatment with PBS only (black line), cetuximab only (blue line), UCB-NK only (green line) and UCB-NK + cetuximab (orange line) were plotted over time to monitor treatment outcome. Statistical differences between groups were calculated using log rank (Mantel-Cox) test and indicated in the figure.