Understanding mechanistic insights into type 1 IFN response mediated by AXL-GAS6 signalling in cancer

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1 Purpose

In this project we will use syngeneic tumor BalbC mouse model to study mechanism that involves AXL overexpression and immune evasion in cancer. We will use Bergenbio's small molecule inhibitor targeting against AXL, bemcentinib, in combination with chemotherapeutics (Doxorubicin or STING agonist) to study Axl-Gas6 signalling. In support of their ongoing pre-clinical program to take bemcentinib into the clinic, we aim to investigate strategies for combination treatment regimes to enhance effects of immune therapies for drug resistant and less immunogenic cancer in our separate efficacy study in the future.

2 Distress

Animals are not expected to suffer pain or discomfort during experimental procedure. Common side effects of the chemotherapeutics (Doxorubicin and STING agonist) used in this study will be noted in the scoring sheet for the animal. Animals that show distress and weight loss will be given saline water ip, and animal condition will be closely monitored for improvement.

3 Expected benefit

Using mice model, we aim to study mechanism that involves AXL overexpression and immune evasion in cancer. This will be followed by an efficacy study and therefore this project will contribute the pre-clinical effort of Bergenbio to use bemcentinib in combination with chemotherapy and immunotherapy.

4 Number of animals, and what kind

In this study we aim to use 300 syngeneic tumor BalbC mouse model. This is a well established model that we have experience with. It is essential to have a sufficient number of animals in each experimental group to get significant results and be able to draw a conclusion. Therefore we plan to include 5 animals/tumors per group to perform the mechanistic study.

5 How to adhere to 3R

Results from in vitro studies, previously performed in vivo studies involving Axl inhibitors have been utilized to only test the hypothesis that have not been previously tested. In house performed experiments and work collaborators have already established the mentioned models in the lab, hence the need for pilot experiments or other large studies to establish the tumor model system is not needed.