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Injection of Syngeneic Murine Melanoma Cells to Determine Their Metastatic Potential in the Lungs
Published on: May 24, 2016
Systemically administered liposome-encapsulated Ad-PEDF potentiates the anti-cancer effects in mouse lung metastasis
Hua-shan Shi1, Li-ping Yang, Wei Wei
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medicine School, Sichuan University, Chengdu, Sichuan, PR China.
Background:
The use of adenoviral vector for gene therapy is still an important strategy for advanced cancers, however, the lack of the requisite coxsackie-adenovirus receptor in cancer cells and host immune response to adenovirus limit the application of adenoviral vector in vivo.
Method:
We designed the antiangiogenic gene therapy with recombinant PEDF adenovirus (Ad-PEDF) encapsulated in cationic liposome (Ad-PEDF/Liposome), and investigated the anti-tumor efficacy of Ad-PEDF/Liposome complex on inhibition of tumor metastasis.
Results:
We found that systemic administration of Ad-PEDF/liposome was well tolerated and resulted in marked suppression of tumor growth, and was more potent than uncoated Ad-PEDF to induce apoptosis in B16-F10 melanoma cells and inhibit murine pulmonary metastases in vivo. After Ad-luciferase was encapsulated with liposome, its distribution decreased in liver and increased in lung. The anti-Ad IgG level of Ad-PEDF/Liposome was significantly lower than Ad-PEDF used alone.
Conclusion:
The present findings provide evidences of systematic administration of cationic liposome-encapsulated Ad-PEDF in pulmonary metastatic melanoma mice model, and show an encouraging therapeutic effect for further exploration and application of more complexes based on liposome-encapsulated adenovirus for more cancers.
Insights
Liposome-encapsulated adenovirus carrying PEDF (Ad-PEDF/Liposome) effectively suppresses melanoma tumor growth and metastasis. This novel gene therapy approach reduces anti-adenovirus immune response, showing promise for treating metastatic cancers.
Area of Science:
- Gene therapy
- Oncology
- Nanomedicine
Background:
- Adenoviral vectors are crucial for cancer gene therapy but face limitations due to low coxsackie-adenovirus receptor expression and host immune responses.
- These limitations restrict the in vivo application of adenoviral vectors for treating advanced cancers.
Purpose of the Study:
- To investigate the anti-tumor efficacy of recombinant PEDF adenovirus (Ad-PEDF) encapsulated in cationic liposomes (Ad-PEDF/Liposome) for inhibiting tumor metastasis.
- To evaluate the safety and immune response of this novel gene delivery system.
Main Methods:
- Designed Ad-PEDF/Liposome complex for antiangiogenic gene therapy.
- Investigated the anti-tumor efficacy and metastasis inhibition in a B16-F10 melanoma mouse model.
- Assessed tumor growth suppression, apoptosis induction, and anti-adenovirus immune response (anti-Ad IgG levels).
Main Results:
- Systemic administration of Ad-PEDF/Liposome was well-tolerated, significantly suppressing tumor growth and inhibiting pulmonary metastases.
- Ad-PEDF/Liposome demonstrated greater potency in inducing apoptosis in melanoma cells compared to uncoated Ad-PEDF.
- Liposome encapsulation altered biodistribution (decreased liver, increased lung uptake for Ad-luciferase) and significantly reduced anti-adenovirus IgG levels.
Conclusions:
- Cationic liposome-encapsulated Ad-PEDF shows encouraging therapeutic effects in a pulmonary metastatic melanoma model.
- This strategy provides evidence for the systemic administration of liposome-adenovirus complexes.
- Further exploration of liposome-encapsulated adenovirus complexes holds potential for treating various cancers.
