title: Conditioning of neonatal pigs using low-dose chemotherapy and murine fetal tissue before murine hybridoma transplantation.
abstract: Immunosuppression, myeloablation, and the use of immunologically immature tissue can overcome major histocompatibility complex barriers by inducing tolerance. With the goal of inducing tolerance to BALB/c-derived murine hybridoma cells producing the 4C6 monoclonal antibody (mAb), we transplanted BALB/c fetal tissue into neonatal pigs during a regimen of low-dose conditioning with busulfan and cyclophosphamide. After the tolerance induction phase, animals received intraperitoneal injections of 4C6 mAb hybridoma cells. Evidence of persistence of injected cells over time was sought by molecular analysis of peripheral blood for the presence of mouse genomic sequences and circulating 4C6 mAb. Persistence of donor polymerase chain reaction signal during the entire duration of the study, detectable mAb titer for 6 weeks, and a twofold increase of mAb concentration after a boost hybridoma infusion was observed in one animal receiving six consecutive administrations of the conditioning regimen. Our model has the distinctive advantage of allowing functional monitoring of engrafted cells for studying tolerance induction strategies. In addition, this model could be the basis for approaches aimed at producing mAbs in tolerized large animals.
authors.affiliation: Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Brescia, Italy.
authors.forename: Georg S
authors.initials: GS
authors.lastname: Wengler
authors.forename: Emiliana
authors.initials: E
authors.lastname: Brocchi
authors.forename: Guerino
authors.initials: G
authors.lastname: Lombardi
authors.forename: Marco
authors.initials: M
authors.lastname: Bailo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bonassi
authors.forename: Davide
authors.initials: D
authors.lastname: Arienti
authors.forename: Alberto
authors.initials: A
authors.lastname: Albertini
authors.forename: Daniele
authors.initials: D
authors.lastname: Alberti
authors.forename: Roberto
authors.initials: R
authors.lastname: Zanini
authors.forename: Ornella
authors.initials: O
authors.lastname: Parolini
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000097:blood; D016332:Fetal Tissue Transplantation / Q000276:immunology*; D006825:Hybridomas / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051379:Mice; D013552:Swine; D019172:Transplantation Conditioning / Q000379:methods*; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents