The Human Immunology and Immunotherapy Initiative is developing a Translational Research Networking and Preclinical Models (TRNPM) facility
at the Anschutz Medical Campus (AMC) to provide a nexus for multiple aspects of translational immunology research. The services provided by this facility will include:
- Enabling and promoting collaboration among investigators along the continuum of clinical-translational-basic research by networking and/or matchmaking clinicians, clinician/scientists, and basic scientists with shared interests;
- Establishing mechanisms that ensure availability of human tissue for research;
- Developing and maintaining preclinical mouse models for testing of candidate therapeutics
The success of translational research on the AMC is tied to the ability to develop novel therapies. In order to do so, investigators need to access primary human cells and tissues affected by inflammation, cancer and autoimmunity (as well as tissues from healthy controls) to fully understand the immunological impact of various therapeutic interventions, and to ultimately bridge the gap to clinical care delivery.
Novel immunotherapies must be tested with sophisticated preclinical models before they can be tried in humans. Ideally, these models should provide a platform where the human immune system can be exposed to experimental and therapeutic manipulations and the readout is meaningful and applicable to humans.
- An ideal model can be found in the form of Human Immune System (HIS) mice. HIS mice are immunodeficient and have been transplanted with a human immune system or some of its components. These models allow us to investigate human immune responses in an experimental setting.
- An important application of HIS mice is the development of HIS onco-mice, which are HIS mice that are additionally engrafted with human tumors. HIS onco-mice are an ideal tool for testing the effects of novel immunotherapies, such as immune checkpoint inhibitors, on human immune responses to tumors.
- HIS mice are also useful for investigating immune responses in the context of autoimmunity and immunological tolerance. Another recently developed HIS mouse model (HCk HIS mice) can be used to determine the propensity of individuals’ B cells to undergo or escape tolerance, a characteristic that can potentially impact the likelihood of autoimmune development.
- Furthermore, HIS mice can be used to study genetic, biologic, and pharmacological therapies to autoimmune and inflammatory responses.
The preclinical model laboratory will be available to advise investigators on the generation and use of genetically engineered mice suitable for their research needs.
The TRNPM facility is currently under the direction of Roberta Pelanda, PhD (Director) and Julie Lang, PhD (Manager, HIS Mouse Core).
- Dr. Lang has a PhD in Immunology and an additional 20 years of bench experience in immunological research. Julie has been working with Dr. Pelanda since 2007 to establish and develop HIS mice in Colorado.
- Jacob ‘Jake’ Barbee was recently hired as a Professional Research Assistant (PRA) to assist Dr. Lang in generating the HIS mice.