After decades of investigation establishing principles in animal models, it has recently become possible to treat and cure some diseases in humans by interventions that target immunological functions. Immunotherapy, described by Science magazine as the Breakthrough of the Year in 2013, has led to major changes in the standard of care for some diseases and is particularly useful in infectious disease, autoimmunity, allergy/asthma, and especially cancer.
The mission of the Human Immunology and Immunotherapy Initiative (HI3) is to develop the infrastructure to create an all-inclusive facility that provides experimental models for the preclinical testing of new candidate therapeutics, reliable immunotherapeutic production, consistent clinical trials research support, and organized immune monitoring capabilities. In addition, the HI3 will train future scientific leaders within the realm of immunotherapy and recruit exemplary faculty to the CU Anschutz medical campus that will complement and enhance existing strengths.
The ultimate goal of the HI3 is to establish preeminence in human immune system-targeted therapies on the CU Anschutz medical campus.
|Checkpoint inhibitors lead to T cell survival and reactivation.
CTLA-4 is a molecule expressed on T cells that when bound by its B-7
ligand serves to inhibit or shut down the T cell. Ipilimumab is a
checkpoint inhibitor that binds to CTLA-4 on the T cell to block
interaction with its B-7 ligand on the antigen-presenting cell (APC). The B-7 ligand alternatively binds to CD28 to result in T cell stimulation and activation.
PD-1 is a molecule expressed on T cells that when bound
by its PD-L1 ligand serves to inhibit the T cell by initiating a
process called ‘programmed cell death’ or cell suicide. Pembrolizumab is
a checkpoint inhibitor that blocks interaction between PD-1 on the T
cell with its ligand PD-L1 on the APC, or in some cases, a cancer cell.
Blocking this interaction allows the T cell to survive and continue to
participate in an immune response directed against killing the targeted
cancer cell. Figure from Ho et al. Cancer Frontiers. April 2015.
|Chimeric antigen receptors create a single specificity for
cells are modified to express a receptor specific for a target antigen
expressed by the tumor cells. The process involves the removal and
isolation of T cells (T) from the cancer patient’s blood and the
molecular modification of the self T cells to express chimeric antigen
receptors (CAR) that recognize cancer-specific antigens. The CAR-T cells are then reinfused into the patient’s body where they attack the tumor in greater numbers. Figure from V. Brower. The Scientist. April 2015.
|Bispecific T cell Engager (BiTE) antibodies redirect T cell specificity.|
BiTEs are antibodies with two specificities; one end is specific for an antigen expressed on a tumor cell and the other end is specific for the CD3 antigen expressed on T cells. The BiTE links the tumor cell to the T cell through CD3, which activates the T cell resulting in destruction of the tumor. Figure from D. Wickramasinghe. Discovery Medicine. September 2013.
Harness the Power of the Human Immune System
Building a strong base for immunotherapy research.
Translational Research Networking and Preclinical Models (TRNPM) facility
The Human Immunology and Immunotherapy Initiative is
developing a Translational Research Networking and Preclinical Models
(TRNPM) facility at the Anschutz Medical Campus... Full story
Transformational Research Award
The Human Immunology and Immunotherapy Initiative was started with a $20 million dollar award from the University of Colorado Anschutz Medical Campus. Full story