Abstract
In allogeneic hematopoietic cell transplantation (allo-HCT), donor lymphocytes play a central therapeutic role in both GvL and immune reconstitution. However the full exploitation of these therapeutic properties is limited by the occurrence of GvHD. Diffierent strategies have been investigated to obtain all the benefits derived from donor lymphocytes while avoiding the risk of GvHD. The genetic engineering of donor lymphocytes with the herpes simplex virus-thymidine kinase (HSV-TK) suicide gene confers the ability to modulate GvHD by in vivo ganciclovir-induced elimination of the transduced cells. The suicide-gene strategy has applications in both donor lymphocyte infusion (DLI) for disease relapse and in add-back infusions after T-cell depleted allo-HCT. TK cell DLI resulted in anti-tumor activity in a relevant proportion of treated patients. Haplo-identical stem cell transplantation (haplo-HCT) is a promising therapeutic option for patients with high risk hematologic malignancies lacking an HLA-matched donor. However, the profound T-cell depletion required to overcome the risk of lethal GvHD has been associated with a marked delayed T-cell recovery with a prolonged risk of post-transplant viral, fungal and other opportunistic infections. TK cell add-backs efficiently promote early immune reconstitution after haplo-HCT and prevent disease relapse providing a unique tool for the control of GvHD. The genetic manipulation of donor lymphocytes with a suicide gene is a promising strategy to increase feasibility and safety of allo-HCT.
| Original language | English |
|---|---|
| Pages (from-to) | 144-149 |
| Number of pages | 6 |
| Journal | Cytotherapy |
| Volume | 7 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2005 |
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Keywords
- Allogeneic transplantation
- Gene therapy
- HSV-TK
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Pharmacology
Cite this
Modulation of GvHD by suicide-gene transduced donor T lymphocytes : Clinical applications in mismatched transplantation. / Ciceri, Fabio; Bonini, C.; Gallo-Stampino, C.; Bordignon, C.
In: Cytotherapy, Vol. 7, No. 2, 2005, p. 144-149.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Modulation of GvHD by suicide-gene transduced donor T lymphocytes
T2 - Clinical applications in mismatched transplantation
AU - Ciceri, Fabio
AU - Bonini, C.
AU - Gallo-Stampino, C.
AU - Bordignon, C.
PY - 2005
Y1 - 2005
N2 - In allogeneic hematopoietic cell transplantation (allo-HCT), donor lymphocytes play a central therapeutic role in both GvL and immune reconstitution. However the full exploitation of these therapeutic properties is limited by the occurrence of GvHD. Diffierent strategies have been investigated to obtain all the benefits derived from donor lymphocytes while avoiding the risk of GvHD. The genetic engineering of donor lymphocytes with the herpes simplex virus-thymidine kinase (HSV-TK) suicide gene confers the ability to modulate GvHD by in vivo ganciclovir-induced elimination of the transduced cells. The suicide-gene strategy has applications in both donor lymphocyte infusion (DLI) for disease relapse and in add-back infusions after T-cell depleted allo-HCT. TK cell DLI resulted in anti-tumor activity in a relevant proportion of treated patients. Haplo-identical stem cell transplantation (haplo-HCT) is a promising therapeutic option for patients with high risk hematologic malignancies lacking an HLA-matched donor. However, the profound T-cell depletion required to overcome the risk of lethal GvHD has been associated with a marked delayed T-cell recovery with a prolonged risk of post-transplant viral, fungal and other opportunistic infections. TK cell add-backs efficiently promote early immune reconstitution after haplo-HCT and prevent disease relapse providing a unique tool for the control of GvHD. The genetic manipulation of donor lymphocytes with a suicide gene is a promising strategy to increase feasibility and safety of allo-HCT.
AB - In allogeneic hematopoietic cell transplantation (allo-HCT), donor lymphocytes play a central therapeutic role in both GvL and immune reconstitution. However the full exploitation of these therapeutic properties is limited by the occurrence of GvHD. Diffierent strategies have been investigated to obtain all the benefits derived from donor lymphocytes while avoiding the risk of GvHD. The genetic engineering of donor lymphocytes with the herpes simplex virus-thymidine kinase (HSV-TK) suicide gene confers the ability to modulate GvHD by in vivo ganciclovir-induced elimination of the transduced cells. The suicide-gene strategy has applications in both donor lymphocyte infusion (DLI) for disease relapse and in add-back infusions after T-cell depleted allo-HCT. TK cell DLI resulted in anti-tumor activity in a relevant proportion of treated patients. Haplo-identical stem cell transplantation (haplo-HCT) is a promising therapeutic option for patients with high risk hematologic malignancies lacking an HLA-matched donor. However, the profound T-cell depletion required to overcome the risk of lethal GvHD has been associated with a marked delayed T-cell recovery with a prolonged risk of post-transplant viral, fungal and other opportunistic infections. TK cell add-backs efficiently promote early immune reconstitution after haplo-HCT and prevent disease relapse providing a unique tool for the control of GvHD. The genetic manipulation of donor lymphocytes with a suicide gene is a promising strategy to increase feasibility and safety of allo-HCT.
KW - Allogeneic transplantation
KW - Gene therapy
KW - HSV-TK
UR - http://www.scopus.com/inward/record.url?scp=21044453633&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21044453633&partnerID=8YFLogxK
U2 - 10.1080/14653240510018136
DO - 10.1080/14653240510018136
M3 - Article
VL - 7
SP - 144
EP - 149
JO - Cytotherapy
JF - Cytotherapy
SN - 1465-3249
IS - 2
ER -