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- W2963291293 abstract "Delayed immune reconstitution and the consequently high rates of leukemia relapse and infectious complications are the main limitations of haploidentical hematopoietic stem cell transplantation. Donor T cell addback can accelerate immune reconstitution but the therapeutic window between graft-versus-host disease and protective immunity is very narrow in the haploidentical transplant setting. Hence, strategies to improve the safety and efficacy of adoptive T cell transfer are particularly relevant in this setting. Adoptive T cell transfer strategies in haploidentical transplantation include the use of antigen-specific T cells, allodepletion and alloanergy induction, immune modulation by the co-infusion of regulatory cell populations, and the use of safety switch gene-modified T cells. Whilst common principles apply, there are features that are unique to haploidentical transplantation, where HLA-mismatching directly impacts on immune reconstitution, and shared versus non-shared HLA-allele can be an important consideration in antigen-specific T cell therapy. This review will also present an update on safety switch gene-modified T cells, which can be conditionally deleted in the event of severe graft-versus-host disease or other adverse events. Herpes Virus Simplex Thymidine Kinase (HSVtk) and inducible caspase-9 (iCasp9) are safety switches that have undergone multicenter studies in haploidentical transplantation with encouraging results. These gene-modified cells, which are trackable long-term, have also provided important insights on the fate of adoptively transferred T cells. In this review, we will discuss the biology of post-transplant T cell immune reconstitution and the impact of HLA-mismatching, and the different cellular therapy strategies that can help accelerate T cell immune reconstitution after haploidentical transplantation." @default.
- W2963291293 created "2019-07-30" @default.
- W2963291293 creator A5024281775 @default.
- W2963291293 creator A5026982969 @default.
- W2963291293 date "2019-08-06" @default.
- W2963291293 modified "2023-10-16" @default.
- W2963291293 title "Adoptive T Cell Therapy Following Haploidentical Hematopoietic Stem Cell Transplantation" @default.
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