Haval Shirwan
Chair in Autoimmune Disease Department of Microbiology and Immunology Director of the Molecular Immunomodulation Program at the Institute for Cellular Therapeutics University of Louisville USA
Title: Exploiting synergy between TNFR and TLR4 signaling for the development of adjuvant systems
Biography
Biography: Haval Shirwan
Abstract
Protein-based subunit vaccines against cancer and infections are attractive because of their safety as well as rapid, cost-effective, and large-scale production. However, they are weekly immunogenic and their immunogenicity is further compromised by various immune evasion mechanisms employed by cancer and chronic infections. Accumulating evidence suggest that prophylactic and therapeutic vaccines may benefit from adjuvants modulating innate, adaptive, and regulatory arms of the immune system. In this context, subunit vaccines efficacy may require formulations that include adjuvants having pleiotropic effects on various cells of the immune system. We have recently generated a novel form the 4-1BBL costimulatory molecule, SA-4-1BBL, having pleiotropic effects on various cells of the immune system. As adjuvant component of subunit-based vaccines, SA-4-1BBL was effective in eradicating tumors in preclinical models. Therapeutic efficacy was associated with a robust increase in T effectors and down-regulation of various immune evasion mechanisms. SA-4-1BBL has recently been used in combination with a TLR4 agonist as adjuvant component of tumor associated antigen-based subunit vaccine in cervical and lung cancer preclinical models with robust therapeutic efficacy. These studies provide a strong rationale for using SA-4-1BBL as a platform to design adjuvant systems for the development of therapeutic vaccines.
