Development of Semliki Forest virus vectors for solid tumor immunotherapy
Purpose of the research:
In this study, we aim at evaluating the efficacy and elucidating the mechanism of action of novel immunotherapeutic strategies against solid tumors based on Semliki Forest virus (SFV) vectors.
Mice studies have shown that delivering cytokines via SFV in the tumor can elicit anti-tumor immune responses, and here we will further examine the mechanism of action for SFV vectors encoding cytokines. Based on our previous research showing the anti-tumor potential of cytokines against cancer, we will examine novel SFV vectors encoding cytokines for the treatment of solid tumors. Previous research has also shown that SFV can be used as a vaccine platform which we will exploit here for vaccination against cancer.
Adverse effects:
Subcutaneous and intramammary tumors are well tolerated by mice and may cause only minimal discomfort. The procedures described in this application have been well established in mice and may cause only minimal discomfort. Intraperitoneal injections may cause mild local irritation but are well tolerated by mice. All the test substances that we intend to apply in this study have not shown any adverse effects in mice.
Predicted benefit:
The experiments in this study will elucidate the effect, function, and mechanism of action of new immunotherapy based on Semliki Forest virus vectors. The experiments will provide proof of concept for new tumor-specific immunotherapy with long term effects in solid tumors.
Total number and type of animals to be used:
A total of 1638 inbred wild-type C57BL/6 mus musculus will be used in this study.
Compliance with 3Rs:
In order to study the therapeutic and immune effects of SFV vectors against cancer use of animals is unavoidable. Immune responses involved in response to cancer immunotherapy are complex, taking place at different immunological sites in vivo and involving a network of cell types and signaling molecules, thus such responses are not possible to simulate in vitro. The tumor models and procedures that will be used in this study are well established and involve minimal discomfort. Moreover, general anesthesia will be applied during procedures to reduce any stress or discomfort that may arise for the animals. Based on statistical calculations and our previous experience with tumor models in mice we will be using the minimal necessary animal number to provide scientifically valid results.
In this study, we aim at evaluating the efficacy and elucidating the mechanism of action of novel immunotherapeutic strategies against solid tumors based on Semliki Forest virus (SFV) vectors.
Mice studies have shown that delivering cytokines via SFV in the tumor can elicit anti-tumor immune responses, and here we will further examine the mechanism of action for SFV vectors encoding cytokines. Based on our previous research showing the anti-tumor potential of cytokines against cancer, we will examine novel SFV vectors encoding cytokines for the treatment of solid tumors. Previous research has also shown that SFV can be used as a vaccine platform which we will exploit here for vaccination against cancer.
Adverse effects:
Subcutaneous and intramammary tumors are well tolerated by mice and may cause only minimal discomfort. The procedures described in this application have been well established in mice and may cause only minimal discomfort. Intraperitoneal injections may cause mild local irritation but are well tolerated by mice. All the test substances that we intend to apply in this study have not shown any adverse effects in mice.
Predicted benefit:
The experiments in this study will elucidate the effect, function, and mechanism of action of new immunotherapy based on Semliki Forest virus vectors. The experiments will provide proof of concept for new tumor-specific immunotherapy with long term effects in solid tumors.
Total number and type of animals to be used:
A total of 1638 inbred wild-type C57BL/6 mus musculus will be used in this study.
Compliance with 3Rs:
In order to study the therapeutic and immune effects of SFV vectors against cancer use of animals is unavoidable. Immune responses involved in response to cancer immunotherapy are complex, taking place at different immunological sites in vivo and involving a network of cell types and signaling molecules, thus such responses are not possible to simulate in vitro. The tumor models and procedures that will be used in this study are well established and involve minimal discomfort. Moreover, general anesthesia will be applied during procedures to reduce any stress or discomfort that may arise for the animals. Based on statistical calculations and our previous experience with tumor models in mice we will be using the minimal necessary animal number to provide scientifically valid results.