Forsøksdyr: Establishment and evaluation of tumor models in immune competent mice


Godkjenningsdato 25.09.2020

Godkjenningsperiode 01.11.2020-01.05.2022

1 Formål
The purpose of these experiments is to establish, evaluate and compare 3 different tumor models that can be grown in healthy (immune competent) mice and therefor be used to study cancer immunotherapy.

2 Skadevirkninger
Mice will be implanted either subcutaneously or orthotopically in either the pancreas (KPC cells), lungs (CMT167 cells - intravenous injection) or in the mammary fat pad (4T1 cells). These are all commonly used models from the literature or collaborators.

3 Forventet nytteverdi
These experiments will be used both to get hands-on experience with the tumor models and the evaluate the baseline immunogenicity of the tumor models. This knowledge will be used to plan and conduct effective experiments on cancer immunotherapies in the future. Immunotherapy is the most promising approach in cancer treatment, at SINTEF we have invested 12 MNOK in developing equipment and knowledge to develop, -and help companies developing novel immunotherapies.

4 Antall dyr og art
A total of 90 animals is applied for, 15 for each tumor model. 5 of each tumor model will receive treatment with PD-1 antibody.
Groups:
1a: KPC subcutaneously. 15 c57/bl6
1b: KPC ortotopically. 15 c57/bl6
2a: CMT167 subcutaneously. 15 c57/bl6
2b: CMT167 orthotopically. 15 c57/bl6
3a: 4T1 subcutaneously. 15 Balb/c
3b: 4T1 orthtopical. 15 Balb/c


5 Hvordan etterleve 3R
At SINTEF department of Biotechnology we do primarily in vitro screening in cell lines to develop drugs which an effort to replace many tests previously done in animals with cell-based assays. However, successful hits from the in vitro screening needs to be checked in a complete immune system.
Replacement: No available replacement is available to measure therapeutic effects on a complex immune system.
Reduction: We have performed a literature search and talked to partners to limit ourselves to only three tumor models. Additionally. The all experiments will be done in two steps where only half of the animals are used in the first round. If those 5 first animals give uniform results, experiments are stopped.
Refinement: These experiments are means to refine future experiments my making sure the tumor models that are used are reproducible and that we have hands-on experience with the models.