Combination of suicide gene therapy with immunestimulating genes for treatment of glioblastoma
1. forsøkets formal
We have developed a new gene therapy for malignant brain tumors (glioblastoma), which shows high killing efficacy and specificity for tumour cells, while it is not toxic for normal cells. The aim of the proposed projectis to combine this gene therapy approach with an immunotherapy. From in vitro coculture experiments with macrophages, we have identified genes, that might convert immunosuppressive macrophages into immune stimulating ones for an efficient anti-tumor response. These genes will be tested in animal experiments tested for the ability to
enhance the therapeutic effect of the suicide gene therapy and to induce an efficient anti-tumor response.
2. forventede skadevirkninger på dyrene
We will implant brain tumor cells into the brain of mice/rats. Tumors will develop and imaged regularly by MRI. Upon tumor development, lentiviral vectors will be injected into the tumors and the animals will be orally treated with Valganciclovir. From our previous experiences, these treatments are well tolerated by the animals. When tumors reach a big size on MRI, animals will be euthanized, preferably before symptoms develop.
3. forventet vitenskapelig eller samfunnsmessig nytteverdi
Glioblastoma is a highly aggressive tumor of the brain with dismal prognosis. Thus new treatment strategies are needed to improve the survival of these patients.
4. Antall dyr og art
C57/BL6; Antall: 466
NOD/SCID mus: 14
5. Erstatning, reduksjon, forbedring, rafinering
This a therapeutic study which needs to be performed in animals. We want to study the impact on the
immune system, which is not possible to do in a culture dish. We will use the number of animals necessary to answer our research question/to measure possible survival differences.
In addition to general anesthesia, we will use local anesthesia (marcain) and we will give pain killer
(temgesic) after operation. We will evaluate the condition of the animals according to a score sheet.
We have developed a new gene therapy for malignant brain tumors (glioblastoma), which shows high killing efficacy and specificity for tumour cells, while it is not toxic for normal cells. The aim of the proposed projectis to combine this gene therapy approach with an immunotherapy. From in vitro coculture experiments with macrophages, we have identified genes, that might convert immunosuppressive macrophages into immune stimulating ones for an efficient anti-tumor response. These genes will be tested in animal experiments tested for the ability to
enhance the therapeutic effect of the suicide gene therapy and to induce an efficient anti-tumor response.
2. forventede skadevirkninger på dyrene
We will implant brain tumor cells into the brain of mice/rats. Tumors will develop and imaged regularly by MRI. Upon tumor development, lentiviral vectors will be injected into the tumors and the animals will be orally treated with Valganciclovir. From our previous experiences, these treatments are well tolerated by the animals. When tumors reach a big size on MRI, animals will be euthanized, preferably before symptoms develop.
3. forventet vitenskapelig eller samfunnsmessig nytteverdi
Glioblastoma is a highly aggressive tumor of the brain with dismal prognosis. Thus new treatment strategies are needed to improve the survival of these patients.
4. Antall dyr og art
C57/BL6; Antall: 466
NOD/SCID mus: 14
5. Erstatning, reduksjon, forbedring, rafinering
This a therapeutic study which needs to be performed in animals. We want to study the impact on the
immune system, which is not possible to do in a culture dish. We will use the number of animals necessary to answer our research question/to measure possible survival differences.
In addition to general anesthesia, we will use local anesthesia (marcain) and we will give pain killer
(temgesic) after operation. We will evaluate the condition of the animals according to a score sheet.