Forsøksdyr: Combination of suicide gene therapy with tumorsuppressive non-coding RNAs for glioblastoma treatment

Godkjenningsdato 03.01.2018

Godkjenningsperiode 03.01.2018-31.12.2020

1. forsøkets formal
We have developed a lentiviral vector for suicide gene therapy (tk) of glioblastoma and showed that this therapy is effective. However, recurrent tumors develop implicating that there is a need to further optimize this treatment. In cell culture experiments we have identified 3 different non-coding RNAs which can sensitize the suicide gene therapy to enhance the killing efficacy of tumor cells. In the present project we want to verify if these non-coding RNAs enhance the therapeutic effect also in vivo.
For this experiment we will implant glioblastoma cells into the brain of nude rats and inject the rats intracranially either with the lentiviral vector that carries tk only or a non-coding RNA candidate only or the vector that carries tk together with a non-coding RNA candidate. Finally we will perform an experiment where we select the two most potent non-coding RNAs to be combined with tk.
2. forventede skadevirkninger på dyrene
We will implant brain tumor cells into the brain of nude 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
Nakne rotter (rnu-/rnu-); Antall: 320
5. Erstatning, reduksjon, forbedring
This a preclinical therapeutic study which has to be performed in animals. The therapeutic efficacy is highly dependent on the tumor microenvironment, which is very complex and cannot be fully mimicked in vitro.