Use of TK-cells in haploidentical hematopoietic stem cell transplantation.
OBJECTIVE
Preserving the beneficial effects of donor T cells against tumor and pathogens while avoiding noxious graft-versus-host disease (GvHD) is the 'holy grail' of allogeneic hematopoietic stem cell transplantation (HSCT). The suicide gene strategy allows the selective elimination of genetically modified donor T cells during GvHD. This review summarizes the results obtained in recent years in the clinical trials of suicide gene therapy using the paradigmatic herpes simplex virus thymidine kinase (TK) suicide gene.


RESULTS
T cells genetically modified to express the TK suicide gene, TK-cells, are safe and preserve most of their functional features; when infused into patients they are capable of conferring substantial protection against infections and tumor recurrence, and are promptly eliminated in the case of GvHD, with complete resolution of the adverse reaction in all treated cases. Unexpectedly, TK-cells also have the indirect effect of promoting patient thymopoiesis, contributing to the renewal of a host-tolerant immune repertoire.


CONCLUSIONS
Suicide gene therapy with TK-cells is a promising approach to overcome the risk of GvHD in allogeneic HSCT, especially from partially incompatible donors, and is currently under evaluation in a multicentric phase III clinical trial.
Experimental Hematology Unit, Division of Regenerative Medicine, Gene Therapy and Stem Cells, Program in Immunology and Bio-Immunotherapy of Cancer; San Raffaele Scientific Institute, Milan, Italy.
Giacomo
G
Oliveira
Raffaella
R
Greco
Maria T
MT
Lupo-Stanghellini
Luca
L
Vago
Chiara
C
Bonini
D000818:Animals; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006561:Herpes Simplex / Q000201:enzymology / Q000235:genetics; D006801:Humans; D013601:T-Lymphocytes / Q000637:transplantation*; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*
D013937:Thymidine Kinase