Molecular-targeted therapy has gained attention because of its high efficacy and weak side effects. Previously, we confirmed that transmembrane 4 superfamily member 5 protein (TM4SF5) can serve as a molecular target to prevent or treat hepatocellular carcinoma (HCC). We recently extended the applica...
Molecular-targeted therapy has gained attention because of its high efficacy and weak side effects. Previously, we confirmed that transmembrane 4 superfamily member 5 protein (TM4SF5) can serve as a molecular target to prevent or treat hepatocellular carcinoma (HCC). We recently extended the application of the peptide vaccine, composed of CpG-DNA, liposome complex, and TM4SF5 peptide, to prevent colon cancer in a mouse model. Here, we first implanted mice with mouse colon cancer cells and then checked therapeutic effects of the vaccine against tumor growth. Immunization with the peptide vaccine resulted in robust production of TM4SF5-specific antibodies, alleviated tumor growth, and reduced survival rate of the tumor-bearing mice. We also found that serum levels of VEGF were markedly reduced in the mice immunized with the peptide vaccine. Therefore, we suggest that the TM4SF5-specific peptide vaccine has a therapeutic effect against colon cancer in a mouse model.
Molecular-targeted therapy has gained attention because of its high efficacy and weak side effects. Previously, we confirmed that transmembrane 4 superfamily member 5 protein (TM4SF5) can serve as a molecular target to prevent or treat hepatocellular carcinoma (HCC). We recently extended the application of the peptide vaccine, composed of CpG-DNA, liposome complex, and TM4SF5 peptide, to prevent colon cancer in a mouse model. Here, we first implanted mice with mouse colon cancer cells and then checked therapeutic effects of the vaccine against tumor growth. Immunization with the peptide vaccine resulted in robust production of TM4SF5-specific antibodies, alleviated tumor growth, and reduced survival rate of the tumor-bearing mice. We also found that serum levels of VEGF were markedly reduced in the mice immunized with the peptide vaccine. Therefore, we suggest that the TM4SF5-specific peptide vaccine has a therapeutic effect against colon cancer in a mouse model.
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제안 방법
In this study, we investigated the therapeutic effect of the TM4SF5-specific peptide against colon cancer in a mouse model and confirmed that immunization with a complex of TM4SF5 peptide and Lipoplex(O) reduced the growth of tumors derived from pre-implanted colon cancer cells in mice.
However, the experiment failed as the mice died before we completed the entire immunization protocol because of the rapid growth of CT-26 cells. Therefore, we modified the experimental procedure to start immunization of the mice with the TM4SF5-specific peptide vaccine three days after CT-26 cells implantation. The immunization interval was also reduced from 10 days to 7 days.
To evaluate the therapeutic anti-tumor activity of the vaccine, we checked the physical phenotype of mice at 20 days after challenge with CT-26 cells followed by three immunizations. The results regarding tumor size (Fig.
To further evaluate the therapeutic efficacy of the vaccine, we assessed the survival rate of the mice bearing colon cancer cell derived tumors until 30 days after implantation with CT-26 cells. As shown in Fig.
대상 데이터
The B cell epitope peptide of human TM4SF5 (TM4SF5R2-3, 138NRTLWDRCEAPPRV151) was selected and produced as previously described (12).
데이터처리
Statistical significance between two samples was evaluated using the Student’s t test (29, 30).
이론/모형
05 was taken as statistically significant. A survival analysis was performed using the Kaplan-Meier method and the results were compared with those of a logrank test.
성능/효과
Overexpression of VEGF has been correlated with poor prognosis of cancer patients (26). In this study, we found that the expression level of serum VEGF was drastically increased after implantation with CT-26 cells and significantly reduced by immunization with the peptide vaccine before and after cancer cell implantation (Fig. 4). Therefore, the peptide vaccine negatively regulates expression of VEGF in the sera.
To evaluate the therapeutic anti-tumor activity of the vaccine, we checked the physical phenotype of mice at 20 days after challenge with CT-26 cells followed by three immunizations. The results regarding tumor size (Fig. 2A), tumor volume (Fig. 2B), and tumor weight (Fig. 2C) revealed that the tumor growth was significantly suppressed in the mice immunized with a complex of TM4SF5 peptide and Lipoplex(O). There was no significant effect in the mice immunized with Lipoplex(O) or TM4SF5 peptide encapsulated in DOPE：CHEMS, which is in agreement with the weak production of TM4SF5-specific antibodies (Fig.
참고문헌 (30)
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