PMID- 7548281
OWN - NLM
STAT- MEDLINE
DCOM- 19951103
LR  - 20131121
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 6
IP  - 6
DP  - 1995 Jun
TI  - Transfer of the HSV-tk gene into donor peripheral blood lymphocytes for in vivo 
      modulation of donor anti-tumor immunity after allogeneic bone marrow 
      transplantation.
PG  - 813-9
AB  - The infusion of donor lymphocytes after allogeneic bone marrow transplantation is 
      a promising therapeutic tool for achieving a graft versus leukemia (GvL) effect 
      in case of leukemic relapse (1-7), and for the treatment of other complications 
      related to the severe immunosuppressive status of transplanted patients, such as 
      Epstein Barr virus-induced lymphoproliferative disorders (EBV-BLPD) (8) or 
      reactivation of CMV infection (9). Although the delay in the administration of T 
      lymphocytes is expected to reduce the risk of severe GvHD, this risk is still 
      present at higher doses of donor T-cells. The transfer of a suicide gene into 
      donor lymphocytes could allow the in vivo selective elimination of cells 
      responsible for severe GvHD. Additionally, under appropriate conditions, it may 
      allow in vivo modulation of donor anti-tumor responses, and to separate GvL from 
      GvHD. Finally, crucial questions concerning survival and function of donor 
      lymphocytes could be answered by their gene marking. Previous studies documented 
      that T lymphocytes are suitable targets for gene transfer through retroviral 
      vectors (10, 11). This protocol has been designed to evaluate in the contest of 
      allogeneic BMT: 1--the safety of increasing doses of donor lymphocytes transduced 
      with a suicide retroviral vector; 2--the efficacy in terms of survival and 
      immunologic potential of donor lymphocytes after in vitro activation, gene 
      transduction, and immunoselection; 3--the possibility of in vivo down regulation 
      of GvHD by the administration of ganciclovir to patients treated by tk-transduced 
      donor lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Bordignon, C
AU  - Bordignon C
AD  - Bone Marrow Transplantation and Gene Therapy Program, Istituto Scientifico H.S. 
      Raffaele, Milano, Italy.
FAU - Bonini, C
AU  - Bonini C
FAU - Verzeletti, S
AU  - Verzeletti S
FAU - Nobili, N
AU  - Nobili N
FAU - Maggioni, D
AU  - Maggioni D
FAU - Traversari, C
AU  - Traversari C
FAU - Giavazzi, R
AU  - Giavazzi R
FAU - Servida, P
AU  - Servida P
FAU - Zappone, E
AU  - Zappone E
FAU - Benazzi, E
AU  - Benazzi E
AU  - et al.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Bone Marrow Transplantation/*immunology
MH  - Clinical Protocols
MH  - Ganciclovir/therapeutic use
MH  - *Gene Transfer Techniques
MH  - *Genetic Therapy
MH  - Genetic Vectors
MH  - Graft vs Host Disease/drug therapy/immunology
MH  - Herpesviridae Infections/etiology/therapy
MH  - Herpesvirus 4, Human
MH  - Humans
MH  - Immunocompromised Host
MH  - Leukemia/immunology/*therapy
MH  - Patient Selection
MH  - Postoperative Complications/therapy
MH  - Retroviridae/genetics
MH  - Simplexvirus/enzymology/*genetics
MH  - *T-Lymphocytes/immunology/transplantation
MH  - Thymidine Kinase/*genetics
MH  - Transplantation, Homologous
MH  - Tumor Virus Infections/etiology/therapy
EDAT- 1995/06/01 00:00
MHDA- 1995/06/01 00:01
CRDT- 1995/06/01 00:00
PHST- 1995/06/01 00:00 [pubmed]
PHST- 1995/06/01 00:01 [medline]
PHST- 1995/06/01 00:00 [entrez]
AID - 10.1089/hum.1995.6.6-813 [doi]
PST - ppublish
SO  - Hum Gene Ther. 1995 Jun;6(6):813-9. doi: 10.1089/hum.1995.6.6-813.