Haval Shirwan, PhD
Haval Shirwan, PhD
Professor, Department of Child Health and Molecular Microbiology and Immunology
Director, Immunomodulation and Translational Research Program
Member, NextGen Precision Health Institue, Child Health Research Institute, and Ellis Fischer Cancer Center
School of Medicine, University of Missouri
Dr. Shirwan is Professor of Child Health and Molecular Microbiology and Immunology in the School of Medicine and a NextGen Precision Health faculty member, University of Missouri-Columbia, MO. He obtained his PhD from the University of California in Santa Barbara, CA, and performed postdoctoral studies at the California Institute of Technology, Pasadena, CA. Before relocating to the University of Missouri-Columbia in 2020, Dr. Shirwan served on the Faculty of various academic institutions in the United States, including Cedars-Sinai Medical Center, Los Angeles, CA, Alleghany University of Health Science, Philadelphia, PA, University of Louisville, Louisville, KY. Dr. Shirwan pioneered the concept of transient and positional display of immunological ligands on the surface of cells and tissues as a safe, practical, and effective alternative to gene therapy for localized immunomodulation with applications to transplantation, autoimmunity, and cancer immunoprevention and immunotherapy. Dr. Shirwan is an inventor with 25 issued patents, founder/co-founder of 3 biotech startups, widely published, and organized and lectured at numerous national/international conferences. He has continuously been funded by federal and non-federal funding agencies and serves on the editorial board of various scientific journals.
Novel Immune Checkpoint Stimulator Invokes Immune Surveillance Mechanism That Protects Against Various Cancer Types
Cancer immunotherapy has shown remarkable efficacy in the clinical and is now a standard of care for various tumors. In particular, immune checkpoint inhibitors, such as PD-1, PD-L1, paved the way for harnessing the power of the immune system to fight cancer. We focused on immune checkpoint stimulators, in particular the CD137 pathway, for cancer treatment as the corollary. The 4-1BB pathway plays a paramount role in the expansion of CD8+ T cells, acquisition of effector function, survival, and establishment of long-term memory that are important to cancer eradication and control of recurrences. The natural ligand, 4-1BBL, functions as a cell membrane protein and has no activity as a soluble protein. We generated an oligomeric soluble form of the ligand, SA-4-1BBL, and demonstrated its therapeutic efficacy as the immune adjuvant component of vaccines for various preclinical cancer models. Unexpectedly, pretreatment of healthy rodents with SA-4-1BBL as a single agent induced an innate immune surveillance mechanism that conferred long-term protection against multiple tumor types, a finding that has not previously been reported in the scientific literature. We are presently using bioinformatics and deep immunophenotyping approaches to elucidate the underlying mechanisms with the intent of discovering additional immune pathways that can be targeted for the development of prophylactic treatments for cancer.