Human Immunology & Immunotherapy Initiative (HI³)
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.
: Human Immunology and Immunotherapy Initiative Fund
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 inhabit 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 liganc On the antigen-presenting cell (APC). The B-7 ligand alternatively binds to CD28 to result in T cell stimulation and activation.
PD-1 As 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 immune response directed against killing the targeted cancer cell. Figure from Ho et al. Cancer Frontiers. April 2015
Chimeric receptors create a single specificity for T cells.
T 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 patients blood and the molecular modification of the self T cells to express chimeric antigen receptors (CAR) That recognized cancer-specific antigens. The Car-T cells 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.