TITLE

Induction of immune tolerance to a transplantation carbohydrate antigen by gene therapy with autologous lymphocytes transduced with adenovirus containing the corresponding glycosyltransferase gene

AUTHOR(S)
Ogawa, H.; Yin, D.-P.; Galili, U.
PUB. DATE
February 2004
SOURCE
Gene Therapy;Feb2004, Vol. 11 Issue 3, p292
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Induction of tolerance to transplantation carbohydrate antigens is of clinical significance in recipients of ABO-incompatible allografts, or of xenografts. The experimental animal model used for studying such tolerance was that of a1,3galactosyltransferase (a1,3GT) knockout (KO) mice, which lacks the a-gal epitope (Gala1-3Galß1-4GlcNAc-R) and which can produce the anti-Gal antibody against it. In contrast, wild-type (WT) mice synthesize the a-gal epitope and are immunotolerant to it. KO lymphocytes transduced in vitro with adenovirus containing the a1,3GT gene (AdaGT) express a-gal epitopes. Administration of such lymphocytes into KO mice resulted in tolerization of naïve and memory anti-Gal B cells. Mice tolerized by AdaGT transduced lymphocytes failed to produce anti-Gal following immunizations with pig kidney membranes (PKM) expressing multiple a-gal epitopes. This tolerance was perpetuated by transplanted syngeneic WT mouse hearts expressing a-gal epitopes. Transplanted WT hearts survived in the tolerized KO mice for at least 100 days, despite repeated PKM immunizations. Control mice receiving lymphocytes transduced with adenovirus lacking the a1,3GT gene were not tolerized, but produced anti-Gal and rejected transplanted WT hearts. This study suggests that autologous lymphocytes transduced with adenovirus containing A or B transferase genes may induce a similar tolerance to blood group antigens in humans.Gene Therapy (2004) 11, 292-301. doi:10.1038/sj.gt.3302178
ACCESSION #
12046771

 

Related Articles

  • B-Cell-Delivered Gene Therapy Induces Functional T Regulatory Cells and Leads to a Loss of Antigen-Specific Effector Cells. Skupsky, Jonathan; Ai-Hong Zhang; Yan Su; Scott, David W. // Molecular Therapy;Aug2010, Vol. 18 Issue 8, p1527 

    Previous reports have shown that B-cell-mediated gene therapy can induce tolerance in several animal models for autoimmune diseases and inhibitory antibody formation in hemophilia A mice. We know from our previous work that the induction of tolerance following B-cell therapy is dependent upon...

  • Chimpanzee-origin adenovirus vectors as vaccine carriers. Tatsis, N.; Tesema, L.; Robinson, E. R.; Giles-Davis, W.; McCoy, K.; Gao, G. P.; Wilson, J. M.; Ertl, H. C. J. // Gene Therapy;Mar2006, Vol. 13 Issue 5, p421 

    Vaccines based on replication-defective adenoviral vectors are being developed for infectious agents and tumor-associated antigens. Early work focused on vaccines derived from a common human serotype of adenovirus, that is, adenovirus of the serotype 5 (AdHu5). Neutralizing antibodies against...

  • Adenovirus targeting to HLA-A1/MAGE-A1-positive tumor cells by fusing a single-chain T-cell receptor with minor capsid protein IX. de Vrij, J.; Uil, T. G.; van den Hengel, S. K.; Cramer, S. J.; Koppers-Lalic, D.; Verweij, M. C.; Wiertz, E. J. H. J.; Vellinga, J.; Willemsen, R. A.; Hoeben, R. C. // Gene Therapy;Jul2008, Vol. 15 Issue 13, p978 

    Adenovirus vectors have great potential in cancer gene therapy. Targeting of cancer-testis (CT) antigens, which are specifically presented at the surface of tumor cells by human leukocyte antigen (HLA) class I molecules, is an attractive option. In this study, a single-chain T-cell receptor...

  • 365. Aerosol Delivery of an Enhanced Helper-Dependent Adenovirus Formulation to Rabbit Lung Using an Intratracheal Catheter Koehler, David R.; Frndova, Helena; Leung, Kitty; Louca, Emily; Palmer, Donna; Ng, Philip; McKerlie, Colin; Cox, Peter; Coates, Allan L.; Hu, Jim // Molecular Therapy;Jun2005, Vol. 11, p142 

    An abstract of the article "Aerosol Delivery of an Enhanced Helper-Dependent Adenovirus Formulation to Rabbit Lung Using an Intratracheal Catheter," by David R. Koehler, Helena Frndova, Kitty Leung, Emily Louca, Donna Palmer, Philip Ng, Colin McKerlie, Peter Cox, and Allan L. Coates is presented.

  • 1008. Characterization of Peripheral Regulatory T Cell Phenotype Generated in Molecular Chimeras by Gene Therapy. Paez-Cortez, Jesus R.; Tian, Chaorui; Iacomini, John // Molecular Therapy;Jun2006, Vol. 13, pS388 

    Introduction. Donor-specific tolerance to MHC class I antigens can be achieved following reconstitution of mice with genetically modified autologous bone marrow cells expressing allogeneic MHC class I genes. The mechanisms by which CD4 T cells that recognize allogeneic antigens through the...

  • Engagement of the B-cell antigen receptor (BCR) allows efficient transduction of ZAP-70-positive primary B-CLL cells by recombinant adeno-associated virus (rAAV) vectors. Kofler, D.M.; Büning, H.; Mayr, C.; Bund, D.; Baumert, J.; Hallek, M.; Wendtner, C.-M. // Gene Therapy;Sep2004, Vol. 11 Issue 18, p1416 

    Engagement of the B-cell antigen receptor (BCR) by crosslinking of the surface immunoglobulin (sIg) homodimer was studied for recombinant adeno-associated virus (rAAV)-mediated gene transfer into B-cell chronic lymphocytic leukaemia (B-CLL) cells. Leukemic cells obtained from 20 patients were...

  • B-Cell Based Gene Therapy for Inducing Tolerance. Carey, Indira; Yan Su; Yufei Jiang; Skupsky, Jonathan; Scott, David W. // Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry;May2007, Vol. 6 Issue 2, p141 

    The ability of B cells to function as tolerogenic antigen presenting cells (APCs) in vitro and in vivo, makes them ideal targets for gene therapy strategies focused on the induction and re-establishment of tolerance. Current therapy methods employ retroviral vectors for infection of B cells or...

  • Use of Mutated Self-Cleaving 2A Peptides as a Molecular Rheostat to Direct Simultaneous Formation of Membrane and Secreted Anti-HIV Immunoglobulins. Yu, Kenneth K.; Aguilar, Kiefer; Tsai, Jonathan; Galimidi, Rachel; Gnanapragasam, Priyanthi; Yang, Lili; Baltimore, David // PLoS ONE;Nov2012, Vol. 7 Issue 11, Special section p1 

    In nature, B cells produce surface immunoglobulin and secreted antibody from the same immunoglobulin gene via alternative splicing of the pre-messenger RNA. Here we present a novel system for genetically programming B cells to direct the simultaneous formation of membrane-bound and secreted...

  • Eradication of hepatoma and colon cancer in mice with Flt3L gene therapy in combination with 5-FU. Sheng Hou; Geng Kou; Xiaoqiang Fan; Hao Wang; Weizhu Qian; Dapeng Zhang; Bohua Li; Jianxin Dai; Jian Zhao; Jing Ma; Jing Li; Birong Lin; Mengchao Wu; Yajun Guo // Cancer Immunology, Immunotherapy;Oct2007, Vol. 56 Issue 10, p1605 

    We developed a recombinant defective adenovirus with an insert of gene encoding extracellular domain of mouse Flt3L (Ad-mFlt3L) under control of cytomegalovirus promoter to investigate the biological efficacy of Flt3L in combination with chemotherapeutical drug, 5-FU, in eliciting an effective...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics