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Updated: Jul 5, 2025
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
Tocilizumab Exerts Anti-Tumor Effects on Colorectal Carcinoma Cell Xenografts Corresponding to Expression Levels of
Yuan-Chiang Chung1,2, Szu-Jung Chen3, Chiu-Chen Huang4
1Department of Surgery, Kuang Tien General Hospital, Taichung 433, Taiwan.
Abstract:
The use of tocilizumab against the interleukin-6 receptor (IL-6R) has been demonstrated as inhibiting the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of tocilizumab on human colorectal carcinoma (CRC) corresponding to IL-6R expression levels remains scarce. To investigate the influence of IL-6R expression, SW480 and HT-29 cells inoculated subcutaneously into NU/NU mice were used as human CRC xenograft models with anti-IL-6R antibody (tocilizumab) therapy. The IL-6R expression levels, histology of CRC growth/invasiveness, and tumor growth-related signaling pathway were estimated by H&E and immunohistochemical staining. SW480 tumor cells with higher IL-6R expression levels showed better responsiveness in tocilizumab therapy than in the treated HT-29 group. Likewise, therapeutic effects of tocilizumab on the proliferative ability with mitotic index and Ki-67 expressions, invasiveness with MMP-9 proteinase expressions, and ERK 1/2 and STAT3 signaling transduction in the SW480 treatment group were superior to the HT-29 treatment group. In light of our results, IL-6R is the key indicator for the efficacy of tocilizumab treatment in CRC xenografts. From the perspective of precision medicine, tumor response to anti-IL-6R antibody therapy could be predicted on the basis of IL-6R expression levels. In this manner, tocilizumab may serve as a targeted and promising anti-CRC therapy.
Insights
Tocilizumab targets the interleukin-6 receptor (IL-6R) to inhibit cancer growth. Higher IL-6R expression in colorectal cancer (CRC) xenografts predicts better response to tocilizumab therapy, suggesting its use in precision medicine.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Tocilizumab, an anti-interleukin-6 receptor (IL-6R) antibody, shows promise in inhibiting diverse cancers.
- Limited data exists on tocilizumab's efficacy in human colorectal carcinoma (CRC) related to IL-6R expression levels.
Purpose of the Study:
- To investigate the influence of IL-6R expression on the anti-tumor effects of tocilizumab in human colorectal carcinoma (CRC) models.
- To evaluate tocilizumab's therapeutic potential as a targeted therapy for CRC based on IL-6R expression.
Main Methods:
- Human CRC xenograft models (SW480 and HT-29) were established in NU/NU mice.
- Mice received anti-IL-6R antibody (tocilizumab) therapy.
- IL-6R expression, CRC histology, invasiveness, and signaling pathways (ERK1/2, STAT3) were assessed using H&E and immunohistochemical staining.
Main Results:
- SW480 cells, with higher IL-6R expression, demonstrated superior responsiveness to tocilizumab compared to HT-29 cells.
- Tocilizumab therapy significantly reduced proliferation (Ki-67, mitotic index) and invasiveness (MMP-9) in SW480 xenografts.
- Enhanced inhibition of ERK1/2 and STAT3 signaling pathways was observed in the SW480 group treated with tocilizumab.
Conclusions:
- IL-6R expression levels are a key indicator for predicting tocilizumab efficacy in colorectal cancer (CRC) xenografts.
- Tocilizumab holds potential as a targeted therapy for CRC, aligning with precision medicine principles.
- Tumor response to anti-IL-6R antibody therapy can be predicted by IL-6R expression levels.
