Study On The ADCC Activity By The Combination Of Cetuximab And NK Cells Against Human Colorectal Cancer Xenografts

Objective: To observe the growth inhibitory effect of the anti-EGFR monoclonal antibodyCetuximab in combination with NK cells in human colorectal cancer cell lines LOVO andSW620xenografts expressing different level of EGFR in nude mice. To explore the ADCCantitumor activity of Cetuximab against human colorectal cancer cells in vivo.Methods: Nude mice xenograft models of colorectal cancer cells LOVO (EGFR+++) orSW620(EGFR-) were established and then randomly divided into6groups: group PBS,Cetuximab, hIgG, NK cells, hIgG+NK cells and Cetuximab+NK cells. Cetuximab or hIgG atthe concentration of1mg/kg were administered by intraperitoneal injection three times a week.NK cells were injected intravenously into the caudal vein at2x106once a week. Inspect theactivities of mice and tumor growth conditions. Measure the tumor dimensions twice a weekand calculate the tumor volume, then describe the tumor growth curve. All the mice weresacrificed3days after the end of treatment and tumors were stripped and weighed. Theantitumor rate was evaluated. Pathological changes in tumor tissues were observed by HEstaining and immunohistochemistry was used to analyse the expression of EGFR and cellproliferation index Ki-67.Results:1. Cetuximab combined with NK cells group showed the greatest growthinhibition on LOVO xenografts (P<0.05), while the other groups had no significant difference(P>0.05); no group in SW620xenografts had significant inhibitory effect (P>0.05).2.Immunohistochemistry showed that LOVO is EGFR positive (+++), and SW620is EGFRnegative (-), which confirmed the expression level of EGFR on selected cell lines in vivo.3.Immunohistochemistry showed the Ki-67labeling index（LI）of LOVO xenografts in groupCetuximab plus NK cells decreased significantly compared to other groups (P<0.05), especiallyless than the PBS group (P<0.01), while no significant difference among other groups (P>0.05); groups in SW620xenografts had no significant difference between each other (P>0.05).The results showed that the combination of Cetuximab plus NK cells could inhibit the cellproliferation of LOVO xenografts. Conclusions: The combination of Cetuximab and NK cells could exert ADCC antitumoractivity to colorectal cancer xenografts in vivo, and the activity was correlated with the level ofEGFR expression on the surface of colorectal cancer cells. The colorectal cancer cells withhigher EGFR expression were more sensitive than those with no EGFR. The biotherapy ofcombinating Cetuximab with NK cells was supposed to be a new treatment to improve thecurative efficacy of Cetuximab for the colorectal cancer patients with high EGFR expression.And the level of EGFR expression on the tumor cells may be a good predictor for the efficacy.