PolyGene scientists publish CAM-PaC pancreatic cancer research findings
Press Release | PolyGene AG
JANUARY 07, 2015
Rümlang, Switzerland: – Scientists working with innovative transgenic research institute PolyGene AG have published their findings on CAM-PaC a novel mouse model targeting pancreatic cancer.
Their research suggests a potential major oncological advance, making sequential genetic manipulation of gene expression and targeting of the host possible for the first time by using an inducible dual-recombinase system that combines flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies. The research also transforms understanding of the role of mast cells in tumor formation.
Lead authors for the paper on ‘A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer’ are Nina Schönhuber, Barbara Seidler, Kathleen Schuck and Christian Veltkamp from the Department of Internal Medicine II at Munich Technical University (Technische Universität München). Altogether, more than 30 researchers collaborated on the project, all from a consortium funded by the EU.
The paper is published in the 20th (October 2014) volume of the journal Nature Medicine.
Sequential genetic manipulation
The paper explains that while genetically engineered mouse models (GEMMs) have dramatically improved understanding of tumor evolution and therapeutic resistance, sequential genetic manipulation of gene expression and targeting of the host remains almost impossible using conventional Cre-loxP–based models.
The authors say they have developed an inducible dual-recombinase system by combining flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies to improve GEMMs of pancreatic cancer.
“This enables investigation of multistep carcinogenesis, genetic manipulation of tumor subpopulations (such as cancer stem cells), selective targeting of the tumor microenvironment and genetic validation of therapeutic targets in autochthonous tumors on a genome-wide scale,” say the authors.
Downgrading mast cells
As a proof of concept, the research team performed tumor cell–autonomous and nonautonomous targeting, recapitulated hallmarks of human multistep carcinogenesis, validated genetic therapy by 3-phosphoinositide-dependent protein kinase inactivation as well as cancer cell depletion.
In the process, they have shown that tumors can form even without the mast cells that previously been thought to be essential oncogenic players, are dispensable for tumor formation.
Schönhuber N., Siedler B., Schuck K, Veltkamp C. (2014), A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer; Nature Medicine 20, pp. 1340–1347, doi:10.1038/nm.3646. Published online 19 October 2014.
PolyGene is a privately owned research institute, located near Zurich, Switzerland, that develops state-of-the-art transgenic animal models of human disease for a worldwide research clientele.
Founded in 2002, PolyGene is run by an international team of scientists with academic and industrial backgrounds, having notable track records in mouse transgenesis as well as in business management.
The focus of the business is on finding and nurturing productive research collaborations that promote scientific advances.
PolyGene is a fully functional production site for the establishment and target validation of transgenic and knockout mouse lines, and also offers co-development opportunities in model building, including rat and rabbit models. PolyGene provides one of the in the world’s most highly regarded professional transgenic services, with over 330 completed customer projects and more than 750 individual mouse lines generated to date.
PolyGene’s strong IP portfolio includes patent rights on innovative antibiotic-inducible expression systems, used exclusively for transgenic service projects, such as the murine recombinant Leukemia Inhibitory Factor ESLIF that PolyGene has developed for the generation of highly chimeric mice.
PolyGene also offers services in speed congenics, inducible expression systems and gene targeting.
PolyGene is configured to contribute actively as an R&D intensive SME partner to EU initiatives such as Horizon 2020, Eurostars, IMI, etc., with an impressive track record of partnering in projects such as CarTarDis (Cardiovascular Target Discovery), SYBIL (studying the genetic causes of skeletal diseases) and TumAdoR (focusing on development of human therapeutic monoclonal antibodies to neutralize immunosuppressive cancer pathways).
Marlen Müller, Project Manager and Marketing, PolyGene AG
Tel: +41 44 818 8806
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