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Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells
Published on: January 6, 2014
Murine renal cell carcinoma: evaluation of a dendritic-cell tumour vaccine
F Chagnon1, L Thompson-Snipes, M Elhilali
1Urology Oncology Research Group, Montreal General Hospital Research Institute, Montreal, Quebec, Canada.
Objective:
To use a murine model of renal cell carcinoma (RCC), Renca, to aid in developing a dendritic cell (DC)-mediated tumour vaccine for RCC; as conventional therapy has been unsuccessful for RCC and therapy using immune modulators has had limited success, novel therapies enhancing further the immune system must be developed.
Materials And Methods:
DCs were obtained from mouse bone marrow enriched for the haematopoietic progenitors, and cultured in the presence of interleukin-4 and granulocyte macrophage-colony stimulating factor. In vivo vaccines and in vitro proliferation assays were used to assess ability of the DCs to present tumour antigen.
Results:
The presence of DCs was confirmed in the cultures by fluorescent-activated cell sorting analysis. In vivo, tumour-bearing animals receiving tumour extract-pulsed DCs as a vaccine showed a two to threefold reduction in tumour growth at day 12 and day 16 but no significant difference at day 28. In vitro, tumour extract-pulsed DCs stimulated significant proliferation of splenocytes from naive animals but not tumour-bearing animals. In addition, splenocytes from tumour-bearing animals had an attenuated immune response in vitro.
Conclusion:
These results show that it is possible to use the DC vaccine to modulate the immune response to achieve an antitumour effect, but further manipulation of the DC vaccine may be needed to overcome the tumour-induced immune suppression.
Insights
Dendritic cell (DC) vaccines showed a temporary reduction in renal cell carcinoma (RCC) tumor growth in mice. Further research is needed to overcome tumor-induced immune suppression for a successful DC-mediated RCC vaccine.
Area of Science:
- Immunology
- Oncology
- Vaccine Development
Background:
- Renal cell carcinoma (RCC) has limited treatment options.
- Conventional therapies and current immune modulators show limited success for RCC.
- Novel therapies are needed to enhance the immune system against RCC.
Purpose of the Study:
- To develop a dendritic cell (DC)-mediated tumor vaccine for RCC using the Renca murine model.
- To assess the ability of DCs to present tumor antigens in vivo and in vitro.
Main Methods:
- DCs were generated from mouse bone marrow progenitors.
- DCs were cultured with IL-4 and GM-CSF.
- In vivo vaccines and in vitro proliferation assays were performed.
Main Results:
- DC presence was confirmed via flow cytometry.
- Tumor extract-pulsed DC vaccines reduced tumor growth by 2-3 fold at days 12 and 16.
- Splenocytes from naive animals showed proliferation with pulsed DCs, but not from tumor-bearing animals.
- Tumor-bearing animals exhibited an attenuated immune response in vitro.
Conclusions:
- DC vaccines can modulate the immune response to achieve an anti-tumor effect.
- Further manipulation of DC vaccines is necessary to overcome tumor-induced immune suppression.
- This study provides a foundation for developing effective DC-mediated RCC vaccines.
