title: A vaccine directed to B cells and produced by cell-free protein synthesis generates potent antilymphoma immunity.
abstract: Clinical studies of idiotype (Id) vaccination in patients with lymphoma have established a correlation between the induced anti-Id antibody responses and favorable clinical outcomes. To streamline the production of an Id vaccine, we engineered a small diabody (Db) molecule containing both a B-cell-targeting moiety (anti-CD19) and a lymphoma Id. This molecule (αCD19-Id) was designed to penetrate lymph nodes and bind to noncognate B cells to form an antigen presentation array. Indeed, the αCD19-Id molecule accumulated on B cells in vivo after s.c. administration. These noncognate B cells, decorated with the diabody, could then stimulate the more rare Id-specific B cells. Peptide epitopes present in the diabody linker augmented the response by activating CD4(+) helper T cells. Consequently, the αCD19-Id molecule induced a robust Id-specific antibody response and protected animals from tumor challenge. Such diabodies are produced in a cell-free protein expression system within hours of amplification of the specific Ig genes from the B-cell tumor. This customized product can now be available to vaccinate patients before they receive other, potentially immunosuppressive, therapies.
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University Medical Center, Stanford University, Stanford, CA 94305, USA.
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Ng
authors.forename: Ming
authors.initials: M
authors.lastname: Jia
authors.forename: Kedar G
authors.initials: KG
authors.lastname: Patel
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Brody
authors.forename: James R
authors.initials: JR
authors.lastname: Swartz
authors.forename: Shoshana
authors.initials: S
authors.lastname: Levy
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D018941:Antigens, CD19 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D005434:Flow Cytometry; D007167:Immunotherapy / Q000379:methods*; D008223:Lymphoma / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D010957:Plasmids / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D018941:Antigens, CD19; D019496:Cancer Vaccines; D017931:DNA Primers