Steven Lawrence Rosinski1, Brad Stone, Scott S Graves, Deborah H Fuller, Stephen C De Rosa, Gregory A Spies, Gregory J Mize, James T Fuller, Rainer Storb. 1. 1 Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA. 2 Department of Medicine, University of Washington, Seattle, WA. 3 The Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA. 4 Department of Microbiology, University of Washington, Seattle, WA. 5 The Washington National Primate Research Center, University of Washington, Seattle, WA. 6 Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA. 7 Department of Laboratory Medicine, University of Washington, Seattle, WA.
Abstract
BACKGROUND: Minor histocompatibility antigen (miHA) vaccines have the potential to augment graft-versus-tumor effects without graft-versus-host disease (GVHD). We used mixed hematopoietic chimerism in the canine model of major histocompatibility complex-matched allogeneic hematopoietic cell transplantation as a platform to develop a miHA vaccination regimen. METHODS: We engineered DNA plasmids and replication-deficient human adenovirus type 5 constructs encoding large sections of canine SMCY and the entire canine SRY gene. RESULTS: Priming with replication-deficient human adenovirus type 5 constructs and boosting with ex vivo plasmid-transfected dendritic cells and cutaneous delivery of plasmids with a particle-mediated epidermal delivery device (PMED) in 2 female dogs induced antigen-specific T-cell responses. Similar responses were observed after a prime-boost vaccine regimen in three female hematopoietic cell transplantation donors. Subsequent donor lymphocyte infusion resulted in a significant change of chimerism in 1 of 3 male recipients without any signs of graft-versus-host disease. The change in chimerism in the recipient occurred in association with the development of CD4+ and CD8+ T-cell responses to the same peptide pools detected in the donor. CONCLUSIONS: These studies describe the first in vivo response to miHA vaccination in a large, outbred animal model without using recipient cells to sensitize the donor. This model provides a platform for ongoing experiments designed to define optimal miHA targets and develop protocols to directly vaccinate the recipient.
BACKGROUND: Minor histocompatibility antigen (miHA) vaccines have the potential to augment graft-versus-tumor effects without graft-versus-host disease (GVHD). We used mixed hematopoietic chimerism in the canine model of major histocompatibility complex-matched allogeneic hematopoietic cell transplantation as a platform to develop a miHA vaccination regimen. METHODS: We engineered DNA plasmids and replication-deficient human adenovirus type 5 constructs encoding large sections of canineSMCY and the entire canineSRY gene. RESULTS: Priming with replication-deficient human adenovirus type 5 constructs and boosting with ex vivo plasmid-transfected dendritic cells and cutaneous delivery of plasmids with a particle-mediated epidermal delivery device (PMED) in 2 female dogs induced antigen-specific T-cell responses. Similar responses were observed after a prime-boost vaccine regimen in three female hematopoietic cell transplantation donors. Subsequent donor lymphocyte infusion resulted in a significant change of chimerism in 1 of 3 male recipients without any signs of graft-versus-host disease. The change in chimerism in the recipient occurred in association with the development of CD4+ and CD8+ T-cell responses to the same peptide pools detected in the donor. CONCLUSIONS: These studies describe the first in vivo response to miHA vaccination in a large, outbred animal model without using recipient cells to sensitize the donor. This model provides a platform for ongoing experiments designed to define optimal miHA targets and develop protocols to directly vaccinate the recipient.
Authors: David B Miklos; Haesook T Kim; Emmanuel Zorn; Ephraim P Hochberg; Luxuan Guo; Alex Mattes-Ritz; Sebastien Viatte; Robert J Soiffer; Joseph H Antin; Jerome Ritz Journal: Blood Date: 2003-09-25 Impact factor: 22.113
Authors: Rob M Verdijk; Antoinette Kloosterman; Jos Pool; Maarten van de Keur; Albert M I H Naipal; Astrid G S van Halteren; Anneke Brand; Tuna Mutis; Els Goulmy Journal: Blood Date: 2003-10-30 Impact factor: 22.113
Authors: D P Granados; A Rodenbrock; J-P Laverdure; C Côté; O Caron-Lizotte; C Carli; H Pearson; V Janelle; C Durette; E Bonneil; D C Roy; J-S Delisle; S Lemieux; P Thibault; C Perreault Journal: Leukemia Date: 2016-02-09 Impact factor: 11.528
Authors: Steven Lawrence Rosinski; Brad Stone; Scott S Graves; Deborah H Fuller; James T Fuller; Rainer Storb Journal: Transplant Direct Date: 2016-04-08