BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Memento EPFL// BEGIN:VEVENT SUMMARY:EPFL BioE Talks SERIES "Controlling Timing and Location in New Va ccine Technologies for Cancer and Infectious Disease" DTSTART:20201026T160000 DTEND:20201026T163000 DTSTAMP:20260510T155251Z UID:8f6273f531c0d1df0e2581f6b444db16d3a3735e7577eb4cce373436 CATEGORIES:Conferences - Seminars DESCRIPTION:Prof. Darrell J. Irvine\, Koch Institute\, Massachusetts Insti tute of Technology\, Cambridge\, MA (USA)\nWEEKLY EPFL BIOE TALKS SERIES\n \n(note that this talk is number one of a double-feature seminar - see det ails of the second talk here)\n\nAbstract:\nThe use of formulation design and materials chemistry to control the timing\, dose\, and location of del ivery of immunostimulatory cues is a powerful strategy to enhance immunity induced by vaccines and cancer immunotherapies.  Two examples of our rec ent work utilizing such approaches will be highlighted: First\, in infecti ous disease vaccines\, the kinetics of antigen availability following immu nization impact many aspects of the antibody response\, but clinically-rel evant methods to control the duration of antigen delivery to lymph nodes i n subunit vaccines are lacking. We conjugated antigens derived from the gp 140 HIV envelope trimer with a phosphoserine (pSer) peptide that binds tig htly to the most common clinical adjuvant\, aluminum hydroxide (Alhydrogel \, or alum). Site specific modification of HIV immunogens with varying num bers of pSer groups allowed self-assembly of these antigens on the surface s of alum particles to be tuned.  Tight binding to alum converted alum it self into a nanoparticle delivery vehicle\, eliciting a 30-fold increase i n germinal center responses and enhanced neutralizing antibody responses r elative to the unmodified antigens. In a second area of research\, we rece ntly developed a strategy to enhance chimeric antigen receptor (CAR) T cel l therapy for cancer\, via targeted delivery of ligands for the CAR T cell to lymph nodes to “vaccine boost” CAR T cells. Small molecules or pep tides are normally rapidly dispersed in the bloodstream following parenter al injection\, but linking these compounds to an albumin-binding lipid moi ety retargets these molecules to lymph nodes. In addition\, these lipid-co njugated molecules can also partition into cell membranes. We hypothesized that by attaching a small molecule\, peptide\, or protein ligand for a ch imeric antigen receptor (CAR) to such albumin-binding lipid tails (forming an “amph-vax” molecule)\, CAR ligands could be delivered efficiently to lymph nodes by albumin and subsequently partition into membranes of res ident antigen presenting cells (APCs)\, thereby co-displaying a CAR T cell ligand from the cell surface together with native cytokine/receptor costi mulation. In syngeneic mouse models of adoptive cell therapy\, we demonstr ated that this approach effectively concentrates CAR T ligands on the surf aces of dendritic cells in lymph nodes\, leading to profound expansion of amph-vax-boosted CAR T cells in vivo.  Amph-vax boosting safely increased the polyfunctionality of CAR T cells in parallel with T cell expansion\, and dramatically enhanced the efficacy of CAR T cell therapy in solid tumo rs.  This concept provides a strategy to regulate the expansion and funct ion of CAR T cells directly in vivo to enhance adoptive cell therapy of ca ncer.\n\nBio:\nDarrell Irvine\, Ph.D.\, is a Professor at the Massachusett s Institute of Technology and an Investigator of the Howard Hughes Medical Institute. He also serves on the steering committee of the Ragon Institut e of MGH\, MIT\, and Harvard.  His research is focused on the application of engineering tools to problems in cellular immunology and the developme nt of new materials for vaccine and drug delivery.  Current efforts are f ocused on problems related to vaccine development for HIV and and immunoth erapy of cancer.  This interdisciplinary work has been recognized in nume rous awards\, including a Beckman Young Investigator award\, an NSF CAREER award\, selection for Technology Review’s ‘TR35’\, election as a Fe llow of the Biomedical Engineering Society\, and appointment as an investi gator of the Howard Hughes Medical Institute.  He is the author of over 7 0 publications\, reviews\, and book chapters and an inventor on numerous p atents.\n\n\n\nZoom link (with registration) for attending remotely: https ://go.epfl.ch/EPFLBioETalks\n\n\nIMPORTANT NOTICE: due to restrictions res ulting from the ongoing Covid-19 situation\, this seminar can be followed via Zoom web-streaming only\, following prior one-time registration throug h the link above. LOCATION:via Zoom web-streaming only\, due to Covid-19 situation https://g o.epfl.ch/EPFLBioETalks https://go.epfl.ch/EPFLBioETalks STATUS:CONFIRMED END:VEVENT END:VCALENDAR