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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.


Related in: MedlinePlus

Tumor weights of (A) LOVO and (B) SW620 xenografts. Differences between groups were determined by the Bonferroni test. nsP>0.05, **P<0.01 and ***P<0.001 compared with the PBS-treated control group (top of bar); nsP>0.05, #P<0.05 and ###P<0.001 compared with the cetuximab plus NK cells group (line connecting bars). PBS, phosphate-buffered saline; hIgG, human immunoglobulin G; NK, natural killer.
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f3-ol-0-0-4835: Tumor weights of (A) LOVO and (B) SW620 xenografts. Differences between groups were determined by the Bonferroni test. nsP>0.05, **P<0.01 and ***P<0.001 compared with the PBS-treated control group (top of bar); nsP>0.05, #P<0.05 and ###P<0.001 compared with the cetuximab plus NK cells group (line connecting bars). PBS, phosphate-buffered saline; hIgG, human immunoglobulin G; NK, natural killer.

Mentions: At the end of experiment, the average LOVO xenograft tumor weight of the cetuximab plus NK cells group was decreased compared with any of the 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=0.047 compared with the NK cells group and P=0.005 compared with the hIgG plus NK cells group), and the inhibition rate was 47.92%, which was ~60% increased compared with the cetuximab or NK cells groups. The cetuximab, NK cells and NK cells plus hIgG groups also demonstrated an antitumor effect compared with PBS group (P=0.0002, P=0.0004 and P=0.0004, respectively), but their tumor weights were increased compared with combination group (P=0.014, P=0.017 and P=0.023, respectively). In SW620 xenograft models, the tumor weight showed no statistical differences among the cetuximab plus NK cell group, NK cells group and NK cells plus hIgG group (P=0.299), but their tumor weights were decreased compared the control group (P=0.008, P=0.004 and P=0.001, respectively). Tumor weight was not affected by cetuximab only in the SW620 cell xenograft models (P=0.430; Fig. 3; Table II).


Cetuximab intensifies the ADCC activity of adoptive NK cells in a nude mouse colorectal cancer xenograft model
Tumor weights of (A) LOVO and (B) SW620 xenografts. Differences between groups were determined by the Bonferroni test. nsP>0.05, **P<0.01 and ***P<0.001 compared with the PBS-treated control group (top of bar); nsP>0.05, #P<0.05 and ###P<0.001 compared with the cetuximab plus NK cells group (line connecting bars). 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

f3-ol-0-0-4835: Tumor weights of (A) LOVO and (B) SW620 xenografts. Differences between groups were determined by the Bonferroni test. nsP>0.05, **P<0.01 and ***P<0.001 compared with the PBS-treated control group (top of bar); nsP>0.05, #P<0.05 and ###P<0.001 compared with the cetuximab plus NK cells group (line connecting bars). PBS, phosphate-buffered saline; hIgG, human immunoglobulin G; NK, natural killer.
Mentions: At the end of experiment, the average LOVO xenograft tumor weight of the cetuximab plus NK cells group was decreased compared with any of the 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=0.047 compared with the NK cells group and P=0.005 compared with the hIgG plus NK cells group), and the inhibition rate was 47.92%, which was ~60% increased compared with the cetuximab or NK cells groups. The cetuximab, NK cells and NK cells plus hIgG groups also demonstrated an antitumor effect compared with PBS group (P=0.0002, P=0.0004 and P=0.0004, respectively), but their tumor weights were increased compared with combination group (P=0.014, P=0.017 and P=0.023, respectively). In SW620 xenograft models, the tumor weight showed no statistical differences among the cetuximab plus NK cell group, NK cells group and NK cells plus hIgG group (P=0.299), but their tumor weights were decreased compared the control group (P=0.008, P=0.004 and P=0.001, respectively). Tumor weight was not affected by cetuximab only in the SW620 cell xenograft models (P=0.430; Fig. 3; Table II).

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