OncoMouse® Studies - Spontaneous Pancreatic OncoMouse Tumor Model
Caliper Discovery Alliances & Services (CDAS) offers multiple tumor models for preclinical cancer research including xenograft, orthotopic and metastasis models. To conduct In vivo anticancer drug efficacy studies CDAS uses bioluminescent (light-emitting) cancer cell lines and Caliper's real-time in vivo imaging IVIS platform. The IVIS technology increases the throughput of vivo efficacy studies since requires fewer test animals and shorter timelines as compared to more conventional animal testing paradigms, thus allowing more compounds to be evaluated for efficacy or deleterious side effects. The combination of bioluminescent cancer cell lines and the IVIS platform offers more and higher quality data; more information can be collected earlier in the development process for those drug candidates that are evaluated in vivo.
To overcome some disadvantages of xenograft tumor models like the use of immuno-compromised mice, CDAS has developed a unique pancreatic OncoMouse model. Through a specific agreement with DuPont Intellectual Assets & Licensing, CDAS is the first and only commercial provider of preclinical in vivo compound efficacy and research studies using spontaneous tumor models linking an activated oncogene with a bioluminescent reporter system. It is now possible for scientists to study drug effects in the more relevant physiological microenvironment context of a non immnuno-compromised animal which will better recapitulate the effect of the drug in humans.
The spontaneous pancreatic OncoMouse tumor model developed by CDAS, namely EL1-luc/EL1-SV40 T-antigen transgenic offers a non-invasive approach for monitoring pancreatic tumor development and provides a relevant biological picture of cancer progression. Proof of concept data are summarized in the abstract below and the full article is available to download in the related information section.
Abstract
We have generated a transgenic mouse that develops spontaneous and bioluminescent pancreatic tumours. Through use of the of the rat elastase I promoter, the expression of firefly luciferase and SV40-T antigens are driven specifically in the acinar cells of the pancreas. The transgenic mice showed pancreas specific basal bioluminescence signal prior to tumor progression and produced increasing light emission from the onset of the pancreatic adenocarcinoma. The latency of tumor development ranged from 10 to more than 20 weeks of age in these mice. Progression of the primary pancreatic cancer was accompanied by emergence of metastatic lesions in the abdominal organs, including liver and fat tissues that are associated with the gastrointestinal track in some of the mice. Interestingly, the male mice seem to develop pancreatic cancers at the younger age than the female mice. We tested the effect of chemotherapy on tumor progression in the EL1-luc/TAg model. Mice treated with rapamycin (5 mg/kg, i.p., three doses per week) starting from the age of 11 weeks showed significant suppression of bioluminescence signal in the pancreas as compared to the vehicle-treated controls.
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Rapamycin treatment suppresses pancreatic tumor development. Bioluminescence images of a representative mouse from rapamycin- and vehicle-treated groups were shown. Treatment started when the mice were 11 weeks of age. |
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A. Bioluminescence imaging of a 10-week-old female EL1-luc/TAg mouse showed pancreas specific signal. Postmortem imaging of the excised pancreas and pancreas-free carcass confirmed that the bioluminescence signals were restricted to the pancreas. B. Imaging of a 12-week-old female EL1-luc/TAg mouse detected increased bioluminescent signal from two hotspots, which showed highly vascularized small tumors. Postmortem imaging confirmed the bioluminescence imaging observation. C. A 19 week-old female mouse showed significant increase of the bioluminescence signal in the pancreatic region. This mouse had the basal level of bioluminescence at 12 week of age. Necropsy analysis revealed a large pancreatic tumor in this mouse and mets in theliver and intestine. D. A 19 week-old female mouse with multiple metastases to the abdomen, as indicated by imaging. Necropsy and imaging ex vivo imaging analysis showed metastases in mesenteric fat and reproductive fat. |
The optical imaging data correlated with the necropsy observations, with the rapamycin treated groups showing lower tumor occurrences as compared to the vehicle treated control groups. Thus the EL1-luc/Tag mouse provides a non-invasive approach for monitoring the spontaneous pancreatic tumor development and offers a convenient tool for evaluation of novel therapeutics against pancreatic cancers. Tumor growth suppression through inhibition of the mTOR pathway further validates this model as clinically relevant.
R&D Benefits of the IVIS technology
Real-time in vivo imaging is designed to provide:
Higher Data Content and Quality — Temporal and spatial data can be collected from the same animal over multiple time points (ie., longitudinal studies). Also, the response to treatment can be assessed without the need for measuring circulating markers or terminal histological assessments. As a consequence, this approach also decreases the statistical error inherent in conventional methodologies, improving data quality.
More Predictive Animal Models — By collecting data from intact, living animals, more accurate predictions can be made earlier in preclinical development process and may help to identify those drug development candidates which will perform better in human clinical trials.
Higher Throughput — Caliper’s proprietary imaging technology requires fewer test animals and shorter timelines as compared to more conventional animal testing paradigms, thus allowing more compounds to be evaluated for efficacy or deleterious side effects
For more information please review the related downloads, email us directly at CDASinvivo@caliperls.com or complete and submit the product inquiry form and a CDAS representative will contact you.
