Imaging activated T cells to study the immunomodulatory potential of radiotherapy
1 Purpose
This is a pilot study in which the imaging potential of the AbOX40 (PET) tracer will be tested in tumor-bearing animal. This tracer is supposed to enable non-invasive and longitudinal imaging of the OX40 receptor, a cell surface marker of T cell activation. Biodistribution of 18FDG will provide additional information regarding the metabolic status of tissues within the animals.
2 Distress
The tumor models that we will use are considered to cause minor discomfort/pain into animals. Animals are not expected to suffer during or after the different imaging methods. In addition, animals will be sedated, kept warm and closely monitored for vital parameters during imaging and treatment procedures. Appropriate analgesics will be administered for retro-orbital injections, and animals will be monitored upon waking. Animals will be humanely euthanized at the end of the protocol.
3 Expected benefit
Currently, there is a pressing need to find alternative treatment strategies to increase response rates of cancer immunotherapies, and to identify biomarkers that may guide patient selection and assist in the evaluation of treatment responses. Radiation therapy has emerged as an appealing partner for cancer immunotherapy, given its dual cytotoxic and immunomodulatory properties. However, additional knowledge on the immunoregulatory potential of clinical radiotherapy is needed to optimize potential synergies and enhance patient benefits. Non-invasive molecular imaging approaches, such as immuno-positron emission tomography (immuno-PET) have the potential to serve as robust biomarker for cancer treatment.
4 Number of animals, and what kind
Pilot studies will comprise in vivo tests of tracer biodistribution and pharmacokinetics in healthy animals, as well as specific targeting in tumor bearing animals (untreated and treated with a CpG vaccine). To increase the robustness and reproducibility of results, identical experiments will be reproduced in two different tumor models comprising two different mouse strains (C57Bl/6 and BALB/c). In total 100 animals. The use of 18F-FDG is limited to the initial pilot studies in a small subset of animals (8 C57BL6 and 8 Balb-c mice).
5 How to adhere to 3R
The techniques applied here contribute to the 3R’s for optimal animal welfare: 1) REDUCTION: preclinical imaging allows serial non-invasive examination and multiple data collection of individual animals. 2) REFINEMENT: pilot studies will be carried out with reduced number of animals to test bio-distribution, clearance, specificity, and imaging properties of the tracers. 3) REPLACEMENT: the use of tumor-bearing animals is unavoidable to test the performance of PET tracers and to conduct longitudinal studies of anti-tumor immune activation.
This is a pilot study in which the imaging potential of the AbOX40 (PET) tracer will be tested in tumor-bearing animal. This tracer is supposed to enable non-invasive and longitudinal imaging of the OX40 receptor, a cell surface marker of T cell activation. Biodistribution of 18FDG will provide additional information regarding the metabolic status of tissues within the animals.
2 Distress
The tumor models that we will use are considered to cause minor discomfort/pain into animals. Animals are not expected to suffer during or after the different imaging methods. In addition, animals will be sedated, kept warm and closely monitored for vital parameters during imaging and treatment procedures. Appropriate analgesics will be administered for retro-orbital injections, and animals will be monitored upon waking. Animals will be humanely euthanized at the end of the protocol.
3 Expected benefit
Currently, there is a pressing need to find alternative treatment strategies to increase response rates of cancer immunotherapies, and to identify biomarkers that may guide patient selection and assist in the evaluation of treatment responses. Radiation therapy has emerged as an appealing partner for cancer immunotherapy, given its dual cytotoxic and immunomodulatory properties. However, additional knowledge on the immunoregulatory potential of clinical radiotherapy is needed to optimize potential synergies and enhance patient benefits. Non-invasive molecular imaging approaches, such as immuno-positron emission tomography (immuno-PET) have the potential to serve as robust biomarker for cancer treatment.
4 Number of animals, and what kind
Pilot studies will comprise in vivo tests of tracer biodistribution and pharmacokinetics in healthy animals, as well as specific targeting in tumor bearing animals (untreated and treated with a CpG vaccine). To increase the robustness and reproducibility of results, identical experiments will be reproduced in two different tumor models comprising two different mouse strains (C57Bl/6 and BALB/c). In total 100 animals. The use of 18F-FDG is limited to the initial pilot studies in a small subset of animals (8 C57BL6 and 8 Balb-c mice).
5 How to adhere to 3R
The techniques applied here contribute to the 3R’s for optimal animal welfare: 1) REDUCTION: preclinical imaging allows serial non-invasive examination and multiple data collection of individual animals. 2) REFINEMENT: pilot studies will be carried out with reduced number of animals to test bio-distribution, clearance, specificity, and imaging properties of the tracers. 3) REPLACEMENT: the use of tumor-bearing animals is unavoidable to test the performance of PET tracers and to conduct longitudinal studies of anti-tumor immune activation.