Potentiation of immune therapy by hyperoxia (elevated oxygen) and Dichloroacetic acid (DCA) in a lung cancer model with and without low calory diet.
1 Purpose: The aim of this study is to explore the anti-tumor potential of combining an approved checkpoint inhibitor (anti-PDl-1- an immunotherapy drug) with either hyperoxia (elevated oxygen) or DCA (a drug that treats various disorders connected to the powerhouse of the cell) in a mouse lung cancer model (Lewis lung cancer). Further, to study the effect of low calorie diet (16 hours colorie restriction). Furthermore, to unravel the fundamental mechanisms in the observed responses.
2 Distress: Animals are not expected to suffer pain during the experimental period. Mice will be injected with Lewis lung cells (LLC) either in the flank or via tail vein injection. Therefore some discomfort will occur due to tumor development. These will be noted in the score sheet for the animal. There is no side effect using neither normobaric and hyperbaric oxygen therapy (HBOT) nor DCA.
3 Expected benefits: Using a mice model, we aim to uncover the mechanisms involved in combining immunotherapy with HBOT and DCA. This is thus a preclinical effort to develop new treatments for lung cancer patients by enhancing the effect of immune therapy.
4 Number of animals and type: We will use 136 C57 black/6 mice to be able to investigate the above mentioned aims.
5 How to adhere to the 3R: As cell culture studies cannot replace the complexity of a mouse model in response to treatment effects, in vivo studies is needed for pre-clinical validation. This is especially true for combined immunotherapy studies.
For the flank model one tumor will be utilized per mouse and all measurements will be used across the experimental time. The personnel performing all procedures necessary for these experiments are highly experienced. The number of animals are also reduced to the minimum for obtaining relevant results.
2 Distress: Animals are not expected to suffer pain during the experimental period. Mice will be injected with Lewis lung cells (LLC) either in the flank or via tail vein injection. Therefore some discomfort will occur due to tumor development. These will be noted in the score sheet for the animal. There is no side effect using neither normobaric and hyperbaric oxygen therapy (HBOT) nor DCA.
3 Expected benefits: Using a mice model, we aim to uncover the mechanisms involved in combining immunotherapy with HBOT and DCA. This is thus a preclinical effort to develop new treatments for lung cancer patients by enhancing the effect of immune therapy.
4 Number of animals and type: We will use 136 C57 black/6 mice to be able to investigate the above mentioned aims.
5 How to adhere to the 3R: As cell culture studies cannot replace the complexity of a mouse model in response to treatment effects, in vivo studies is needed for pre-clinical validation. This is especially true for combined immunotherapy studies.
For the flank model one tumor will be utilized per mouse and all measurements will be used across the experimental time. The personnel performing all procedures necessary for these experiments are highly experienced. The number of animals are also reduced to the minimum for obtaining relevant results.