Adoptive immunotherapy for leukemia: donor lymphocytes transduced with the herpes simplex thymidine kinase gene for remission induction. HGTRI 0103. Hum Gene Ther 1998 Jan 01;9(1):115-34
Date
02/11/1998Pubmed ID
9458247DOI
10.1089/hum.1998.9.1-115Scopus ID
2-s2.0-0031975258 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
This study will evaluate the safety and efficacy of allogenic donor lymphocyte infusions in patients who have relapsed hematologic malignancies after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease (GvHD). We hypothesize that a retroviral vector containing the Herpes simplex thymidine kinase (HStk) gene will allow for retention of the anti-leukemia response of transfused donor lymphocytes while allowing for the adverse effects of GVHD to be mitigated. Patients with relapsed hematologic malignancies after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The Herpes Simplex thymidine kinase (HStk) gene will be transduced into the cells ex vivo using LTKOSN. 1 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effect of graft versus host disease, if it develops.
Author List
Link CJ Jr, Burt RK, Traynor AE, Drobyski WR, Seregina T, Levy JP, Gordon L, Rosen ST, Burns WH, Camitta B, Casper J, Horowitz M, Juckett M, Lawton C, Margolis D, Pietryga D, Rowlings P, Taylor C, Furtado M, Stefka J, Gupta-Burt S, Kaiser H, Vesole DHAuthors
William R. Drobyski MD Professor in the Medicine department at Medical College of WisconsinMary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
David A. Margolis MD Chair, Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Clinical ProtocolsEvaluation Studies as Topic
Genetic Vectors
Humans
Immunotherapy, Adoptive
Leukemia, Lymphoid
Lymphocytes
Patient Selection
Remission Induction
Simplexvirus
Thymidine Kinase