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Published on: May 10, 2024
[Effect of lenti-mCCL20 on the growth of mouse tumor]
Hong-xia Li1, Ping Chen, Lian Wang
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Objects:
We aim at inducing a potent antitumor immune response via CCL20 expressing in situ tumor.
Methods:
We constructed a recombinant lentivirus encoding mouse CCL20 cDNA and transduced the mouse mesenchymal stem cells (mMSCs) in vitro, and then selected the transfected cells to get a stable mixed mCCL20-expressing pool (named as lenti-mCCL20-mMSCs) with blasticidin. By the same means, we produced another pool named as lenti-null-mMSCs. The CT26 was mixed with lenti-mCCL20-mMSC and inoculated sc into the left hinder back of BALB/c mouse. And also the CT26 was alone, or mixed with lenti-null-mMSCs or parent mMSCs, and then inoculated sc into BALB/c mice serving as controls.
Results:
We got a lenti-mCCL20-mMSCs expression construct. It was shown that mCCL20 increased intratumoral lymphocytes infiltration and facilitated tumor growth in syngeneic murine tumor model.
Conclusions:
CCL20 expressing in situ tumor enhances intratumoral lymphocytes infiltration but facilitates tumor growth. However, the mechanism involved remains to be further elucidated.
Insights
Chemokine (C-C motif) ligand 20 (CCL20) expression in situ enhances intratumoral lymphocyte infiltration but also promotes tumor growth in a murine model. Further research is needed to understand the underlying mechanisms.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- The development of effective cancer immunotherapies is a critical area of research.
- Targeting chemokine signaling pathways presents a potential strategy for modulating the tumor microenvironment.
Purpose of the Study:
- To investigate the effect of in situ tumor expression of chemokine (C-C motif) ligand 20 (CCL20) on antitumor immune responses.
- To evaluate the potential of CCL20-engineered mesenchymal stem cells (mMSCs) as a therapeutic approach.
Main Methods:
- Constructed a recombinant lentivirus encoding mouse CCL20 cDNA for transduction of mMSCs.
- Generated stable mCCL20-expressing mMSCs (lenti-mCCL20-mMSCs) and control mMSCs (lenti-null-mMSCs).
- Inoculated CT26 tumor cells mixed with lenti-mCCL20-mMSCs or control cells into BALB/c mice.
Main Results:
- Successfully generated lenti-mCCL20-mMSCs expression construct.
- CCL20 expression led to increased intratumoral lymphocyte infiltration.
- Observed facilitated tumor growth in the syngeneic murine tumor model.
Conclusions:
- In situ tumor expression of CCL20 enhances intratumoral lymphocyte infiltration.
- CCL20 expression paradoxically facilitates tumor growth.
- The precise mechanisms underlying these effects require further investigation.
