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Cetuximab intensifies the ADCC activity of adoptive NK cells in a nude mouse colorectal cancer xenograft model

View Article: PubMed Central - PubMed

ABSTRACT

Natural killer (NK) cells, discovered ~40 years ago, are believed to be the most effective cytotoxic lymphocytes to counteract cancer; however, adoptive NK cell therapy in vivo has encountered certain limitations, including a lack of specificity. The drug cetuximab can mediate antibody dependent cell mediated cytotoxicity (ADCC) activity through NK cells in vivo, and has been approved for the first-line treatment of epidermal growth factor receptor (EGFR)-positive metastatic colorectal cancer (CRC). However, the ADCC activity of adoptive NK cells, induced by cetuximab in a nude mouse CRC xenograft model, has not been previously reported. The aim of the present study was to explore the ADCC activity of cetuximab combined with adoptive NK cells in CRC xenograft models with various EGFR expressions. The nude mouse xenograft models were established by subcutaneously injecting LOVO or SW620 cells. The mice were then randomly divided into 6 groups: Phosphate-buffered saline, cetuximab, human immunoglobulin G (hIgG), NK cells, hIgG plus NK cells and cetuximab plus NK cells. The ADCC antitumor activity was evaluated in these CRC models. The results indicated that the cetuximab plus NK cells group showed the greatest tumor inhibition effect compared with the NK cells group in LOVO xenograft tumor models with positive EGFR expression. However, the combination of cetuximab and NK cells did not show a stronger tumor inhibitory effect against the SW620 xenograft tumor models compared with the efficiency of NK cells. In conclusion, cetuximab could intensify the ADCC antitumor activity of adoptive NK cells towards CRC with an increased EGFR expression. The combination of cetuximab and NK cells may be a potential immunotherapy for metastatic CRC patients with positive EGFR expression.

No MeSH data available.


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Tumor growth curves of (A) LOVO and (B) SW620 xenografts. PBS, phosphate-buffered saline; hIgG, human immunoglobulin G; NK, natural killer.
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f2-ol-0-0-4835: Tumor growth curves of (A) LOVO and (B) SW620 xenografts. PBS, phosphate-buffered saline; hIgG, human immunoglobulin G; NK, natural killer.

Mentions: The tumor growth curve showed that the LOVO xenograft underwent a growth restriction following the injection of cetuximab plus NK cells, and the average tumor volume was evidently decreased compared with other groups (P<0.0001 compared with the PBS group, P<0.0001 compared with the hIgG group, P=0.004 compared with the cetuximab group, P=0.02 compared with the NK cells group and P=0.01 compared with the hIgG plus NK cells group). Furthermore, the tumor growth was also inhibited in the cetuximab only, NK cells only and NK cells plus hIgG groups, with similar inhibitory effects in each (P=0.113). The tumor volume was inhibited, but no statistically significantly difference was found, among the cetuximab plus NK cells, NK cells and NK cells plus hIgG groups of the SW620 xenograft models (P=0.374), and tumor growth was not inhibited in the cetuximab group (Fig. 2).


Cetuximab intensifies the ADCC activity of adoptive NK cells in a nude mouse colorectal cancer xenograft model
Tumor growth curves of (A) LOVO and (B) SW620 xenografts. PBS, phosphate-buffered saline; hIgG, human immunoglobulin G; NK, natural killer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998150&req=5

f2-ol-0-0-4835: Tumor growth curves of (A) LOVO and (B) SW620 xenografts. PBS, phosphate-buffered saline; hIgG, human immunoglobulin G; NK, natural killer.
Mentions: The tumor growth curve showed that the LOVO xenograft underwent a growth restriction following the injection of cetuximab plus NK cells, and the average tumor volume was evidently decreased compared with other groups (P<0.0001 compared with the PBS group, P<0.0001 compared with the hIgG group, P=0.004 compared with the cetuximab group, P=0.02 compared with the NK cells group and P=0.01 compared with the hIgG plus NK cells group). Furthermore, the tumor growth was also inhibited in the cetuximab only, NK cells only and NK cells plus hIgG groups, with similar inhibitory effects in each (P=0.113). The tumor volume was inhibited, but no statistically significantly difference was found, among the cetuximab plus NK cells, NK cells and NK cells plus hIgG groups of the SW620 xenograft models (P=0.374), and tumor growth was not inhibited in the cetuximab group (Fig. 2).

View Article: PubMed Central - PubMed

ABSTRACT

Natural killer (NK) cells, discovered ~40 years ago, are believed to be the most effective cytotoxic lymphocytes to counteract cancer; however, adoptive NK cell therapy in vivo has encountered certain limitations, including a lack of specificity. The drug cetuximab can mediate antibody dependent cell mediated cytotoxicity (ADCC) activity through NK cells in vivo, and has been approved for the first-line treatment of epidermal growth factor receptor (EGFR)-positive metastatic colorectal cancer (CRC). However, the ADCC activity of adoptive NK cells, induced by cetuximab in a nude mouse CRC xenograft model, has not been previously reported. The aim of the present study was to explore the ADCC activity of cetuximab combined with adoptive NK cells in CRC xenograft models with various EGFR expressions. The nude mouse xenograft models were established by subcutaneously injecting LOVO or SW620 cells. The mice were then randomly divided into 6 groups: Phosphate-buffered saline, cetuximab, human immunoglobulin G (hIgG), NK cells, hIgG plus NK cells and cetuximab plus NK cells. The ADCC antitumor activity was evaluated in these CRC models. The results indicated that the cetuximab plus NK cells group showed the greatest tumor inhibition effect compared with the NK cells group in LOVO xenograft tumor models with positive EGFR expression. However, the combination of cetuximab and NK cells did not show a stronger tumor inhibitory effect against the SW620 xenograft tumor models compared with the efficiency of NK cells. In conclusion, cetuximab could intensify the ADCC antitumor activity of adoptive NK cells towards CRC with an increased EGFR expression. The combination of cetuximab and NK cells may be a potential immunotherapy for metastatic CRC patients with positive EGFR expression.

No MeSH data available.


Related in: MedlinePlus