title: Construction and Immunogenicity Testing of Whole Recombinant Yeast-Based T-Cell Vaccines.
abstract: GlobeImmune's Tarmogen(®) immunotherapy platform utilizes recombinant Saccharomyces cerevisiae yeast as a vaccine vector to deliver heterologous antigens for activation of disease-specific, targeted cellular immunity. The vaccines elicit immune-mediated killing of target cells expressing viral and cancer antigens in vivo via a CD8(+) CTL-mediated mechanism. Tarmogens are not neutralized by host immune responses and can be administered repeatedly to boost antigen-specific immunity. Production of the vaccines yields stable off-the-shelf products that avoid the need for patient-specific manufacturing found with other immunotherapeutic approaches. Tarmogens for the treatment of chronic hepatitis B and C and various cancers were well tolerated and immunogenic in phase 1 and 2 clinical trials encompassing >600 subjects. The platform is being widely utilized in basic vaccine research and the most rapid path to success in these endeavors follows from optimal immunoassay selection and execution. This chapter provides detailed methods for the construction and preclinical immunogenicity testing of yeast-based immunotherapeutic products to support the rapid and efficient use of this versatile technology.
authors.affiliation: GlobeImmune, Inc., 1450 Infinite Drive, Louisville, CO, 80027, USA. tom.king@globeimmune.com.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: King
authors.affiliation: GlobeImmune, Inc., 1450 Infinite Drive, Louisville, CO, 80027, USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Guo
authors.affiliation: GlobeImmune, Inc., 1450 Infinite Drive, Louisville, CO, 80027, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hermreck
authors.affiliation: GlobeImmune, Inc., 1450 Infinite Drive, Louisville, CO, 80027, USA.|Integrated Department of Immunology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Bellgrau
authors.affiliation: GlobeImmune, Inc., 1450 Infinite Drive, Louisville, CO, 80027, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Rodell
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D007114:Immunization; D051379:Mice; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*
chemical_list: D014614:Vaccines, Synthetic
keywords: CD4 T cells; CD8 T cells; Cellular immunity; Immunotherapy; Recombinant yeast; Tarmogen®; Th17 cells; Therapeutic vaccine