Forsøksdyr: Optimized activation of macrophages for cancer immunotherapy

Godkjenningsdato 29.06.2020

Godkjenningsperiode 01.07.2020-30.06.2024

Purpose of the research:
In this project, we aim at evaluating the efficacy of novel immunotherapeutic strategies against cancer based on optimized activation of a type of immune cells called macrophages. We have previously performed a number of in vitro studies to define the rules how to render macrophages able to kill cancer cells. We now plan to perform preclinical evaluation of the antitumor efficacy of these protocols in vivo in mouse models for breast, lung and colorectal cancer.

Adverse effects:
Subcutaneous and intramammary tumors are well tolerated by mice and may cause only minimal discomfort. The procedures described in this application have been well established in mice and may cause only minimal discomfort. All the test substances that we intend to apply in this study have not shown, or are not expected to show, any adverse effects in mice.

Predicted benefit:
The experiments in this study will test the efficacy of potential new immunotherapeutics for cancer based on macrophage activation. The experiments will provide proof of concept for new immunotherapies in preclinical mouse models. This research may potentially lead to novel treatment modalities for patients with cancer.

Total number and type of animals to be used:
A total of 3207 inbred wild-type C57BL/6 mus musculus will be used in this study.

Compliance with 3Rs:
In order to study the therapeutic and immune effects of macrophage activation against cancer, the use of animals is unavoidable. Immune responses involved in response to cancer immunotherapy are complex, taking place at different immunological sites in vivo and involving a network of cell types and signaling molecules, thus such responses are not possible to simulate in vitro. The tumor models and procedures that will be used in this study are well established and involve minimal discomfort. Moreover, general anesthesia will be applied during procedures to reduce any stress or discomfort that may arise for the animals. Based on statistical calculations and our previous experience with tumor models in mice, we will be using the minimal necessary animal number to provide scientifically valid results. In order to reduce the number of experimental groups, we have performed extensive in vitro studies with cell cultures in order to identify the most promising compounds for activation of macrophages for cancer elimination. In this way, we can use as few mice as possible and any observed therapeutic failure in mice will be because of the failure of treatment efficacy in vivo, and not because of defective reagents or inappropriate protocols to activate macrophages. General mouse health will be monitored daily and a refined score sheet will be used when approaching humane endpoints to observe the need for euthanizing animals before animal health status is diminished.