T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation

被引:1
作者
Gaudeaux, Pierre [1 ,2 ]
Moirangthem, Ranjita Devi [1 ]
Bauquet, Aurelie [2 ]
Simons, Laura [2 ,3 ]
Joshi, Akshay [1 ]
Cavazzana, Marina [2 ,4 ,5 ,6 ]
Negre, Olivier [2 ]
Soheili, Shabi [2 ]
Andre, Isabelle [1 ]
机构
[1] Univ Paris Cite, Imagine Inst, Human Lymphohematopoiesis Lab, INSERM,UMR 1163, Paris, France
[2] Smart Immune, Paris, France
[3] Heidelberg Univ, Dept Med 5 Hematol Oncol & Rheumatol, Heidelberg, Germany
[4] Hop Univ Necker Enfants Malad, Assistance Publ Hop Paris, Grp Hosp Paris Ctr, Dept Biotherapy, Paris, France
[5] Grp Hosp Univ Paris Cite, Assistance Publ Hop Paris, Biotherapy Clin Invest Ctr,INSERM CIC 1416, Paris, France
[6] Univ Paris Cite, Imagine Inst, Paris, France
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
基金
欧盟地平线“2020”;
关键词
allogeneic hematopoietic stem cell transplantation; T-cells; immune reconstitution; T-cell progenitors; immunotherapy; thymus; immunodeficient; immunocompromised; INNATE LYMPHOID-CELLS; EPITHELIAL-CELLS; IN-VITRO; IMMUNE RECONSTITUTION; ADOPTIVE TRANSFER; CULTURE-SYSTEM; DIFFERENTIATION; EXPRESSION; INDUCTION; VIVO;
D O I
10.3389/fimmu.2022.956919
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of preference for numerous malignant and non-malignant hemopathies. The outcome of this approach is significantly hampered by not only graft-versus-host disease (GvHD), but also infections and relapses that may occur because of persistent T-cell immunodeficiency following transplantation. Reconstitution of a functional T-cell repertoire can take more than 1 year. Thus, the major challenge in the management of allogeneic HSCT relies on the possibility of shortening the window of immune deficiency through the acceleration of T-cell recovery, with diverse, self-tolerant, and naive T cells resulting from de novo thymopoiesis from the donor cells. In this context, adoptive transfer of cell populations that can give rise to mature T cells faster than HSCs while maintaining a safety profile compatible with clinical use is of major interest. In this review, we summarize current advances in the characterization of thymus seeding progenitors, and their ex vivo generated counterparts, T-cell progenitors. Transplantation of the latter has been identified as a worthwhile approach to shorten the period of immune deficiency in patients following allogeneic HSCT, and to fulfill the clinical objective of reducing morbimortality due to infections and relapses. We further discuss current opportunities for T-cell progenitor-based therapy manufacturing, including iPSC cell sources and off-the-shelf strategies. These opportunities will be analyzed in the light of results from ongoing clinical studies involving T-cell progenitors.
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页数:9
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