Faculty Collaboration Database

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

02/11/1998

Pubmed ID

9458247

DOI

10.1089/hum.1998.9.1-115

Scopus ID

2-s2.0-0031975258 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

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 DH

Authors

Bruce m. Camitta Professor in the Pediatrics department at Medical College of Wisconsin
James Casper MD Emeritus Professor in the Pediatrics department at Medical College of Wisconsin
William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MS, MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Colleen A. Lawton MD Emeritus Professor in the Radiation Oncology department at Medical College of Wisconsin
David A. Margolis BA, MD Chair, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Clinical Protocols
Evaluation Studies as Topic
Genetic Vectors
Humans
Immunotherapy, Adoptive
Leukemia, Lymphoid
Lymphocytes
Patient Selection
Remission Induction
Simplexvirus
Thymidine Kinase