title: Generation of primary peptide-specific CD8+ cytotoxic T-lymphocytes in vitro using allogeneic dendritic cells.
abstract: Dendritic cells (DC) are potent antigen-presenting cells (APC) capable of inducing strong T-cell-mediated immunity. Infusion of lymphoma-specific antigen-loaded autologous DC has been demonstrated to result in the generation of antigen-specific immunity and reduction in tumor burden in B-cell lymphoma patients. Cellular immunotherapy employing antigen-loaded DC could have a potential therapeutic impact in tumors and viral infections, including HIV infection. However, DC in HIV-infected individuals and breast cancer patients are believed to be functionally defective. Therefore, the potential of using allogeneic DC offers significant implications for DC immunotherapy in AIDS and immunocompromised cancer patients. To explore the potential of allogeneic DC therapy in vivo, we tested the ability of allogeneic DC to generate primary peptide-specific CD8+ cytotoxic T-lymphocyte (CTL) responses in vitro. Our results indicate that DC from HLA class I-matched individuals elicit primary immune responses in vitro using viral peptides as naive antigens. A primary peptide-specific immune response could also be detected even when only one HLA allele (HLA-A*0201) was matched between the allogeneic DC and T-lymphocytes. The ability to generate primary peptide-specific responses in vitro is strongly indicative of the in vivo therapeutic potential of allogeneic DC.
authors.affiliation: Activated Cell Therapy, Inc., Mountain View, CA 94043, USA.
authors.forename: M V
authors.initials: MV
authors.lastname: Peshwa
authors.forename: C
authors.initials: C
authors.lastname: Benike
authors.forename: M
authors.initials: M
authors.lastname: Dupuis
authors.forename: S K
authors.initials: SK
authors.lastname: Kundu
authors.forename: E G
authors.initials: EG
authors.lastname: Engleman
authors.forename: T C
authors.initials: TC
authors.lastname: Merigan
authors.forename: W C
authors.initials: WC
authors.lastname: van Schooten
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017690:Cell Transplantation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D005260:Female; D016356:Gene Products, tax / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy; D015234:HLA-A Antigens; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D007519:Isoantigens; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D016356:Gene Products, tax; D015234:HLA-A Antigens; D007519:Isoantigens; D009842:Oligopeptides