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HA-1-targeted T cell receptor (TCR) T cell therapy for recurrent leukemia after hematopoietic stem cell transplantation

Krakow, Elizabeth F. ; Brault, Michelle ; Summers, Corinne ; Cunningham, Tanya M. ; Biernacki, Melinda A. ; Black, R. Graeme ; Woodward, Kyle B. ; Vartanian, Nicole ; Kanaan, Sami B. ; Yeh, Albert C. ; Dossa, Robson G. ; Bar, Merav ; Cassaday, Ryan D. ; Dahlberg, Ann ; Till, Brian G. ; Denker, Andrew E. ; Yeung, Cecilia C.S. ; Gooley, Ted A. ; Maloney, David G. ; Riddell, Stanley R. ; Greenberg, Philip D. ; Chapuis, Aude G. ; Newell, Evan W. ; Furlan, Scott N. ; Bleakley, Marie

Blood, 2024-04 [Periódico revisado por pares]

United States: Elsevier Inc

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  • Título:
    HA-1-targeted T cell receptor (TCR) T cell therapy for recurrent leukemia after hematopoietic stem cell transplantation
  • Autor: Krakow, Elizabeth F. ; Brault, Michelle ; Summers, Corinne ; Cunningham, Tanya M. ; Biernacki, Melinda A. ; Black, R. Graeme ; Woodward, Kyle B. ; Vartanian, Nicole ; Kanaan, Sami B. ; Yeh, Albert C. ; Dossa, Robson G. ; Bar, Merav ; Cassaday, Ryan D. ; Dahlberg, Ann ; Till, Brian G. ; Denker, Andrew E. ; Yeung, Cecilia C.S. ; Gooley, Ted A. ; Maloney, David G. ; Riddell, Stanley R. ; Greenberg, Philip D. ; Chapuis, Aude G. ; Newell, Evan W. ; Furlan, Scott N. ; Bleakley, Marie
  • É parte de: Blood, 2024-04
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
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  • Descrição: •This is the first reported trial to use a class I-restricted TCR and a CD8 co-receptor to enable antigen-specific CD4+ T cell function.•Primary endpoints of feasibility and tolerability were met in a phase I clinical trial of HA-1 TCR-T for recurrent leukemia post-HCT. Relapse is the leading cause of death after allogeneic hematopoietic stem cell transplantation (HCT) for leukemia. T cells engineered by gene transfer to express T cell receptors (TCR; TCR-T) specific for hematopoietic-restricted minor histocompatibility (H) antigens may provide a potent selective anti-leukemic effect post-HCT. We conducted a phase I clinical trial employing a novel TCR-T product targeting the minor H antigen HA-1 to treat or consolidate treatment of persistent or recurrent leukemia and myeloid neoplasms. The primary objective was to evaluate the feasibility and safety of administration of HA-1 TCR-T post-HCT. CD8+ and CD4+ T cells expressing the HA-1 TCR and a CD8-co-receptor were successfully manufactured from HA-1 disparate HCT donors. One or more infusions of HA-1 TCR-T following lymphodepleting chemotherapy were administered to nine HCT recipients who had developed disease recurrence post-HCT. TCR-T cells expanded and persisted in vivo after adoptive transfer. No dose-limiting toxicities occurred. Although the study was not designed to assess efficacy, four patients achieved or maintained complete remissions following lymphodepletion and HA-1 TCR-T, with one ongoing at >2 years. Single-cell RNA sequencing of relapsing/progressive leukemia after TCR-T therapy identified upregulated molecules associated with T cell dysfunction or cancer cell survival. HA-1 TCR-T therapy appears feasible and safe and shows preliminary signals of efficacy. This clinical trial is registered at clinicaltrials.gov as NCT03326921.
  • Editor: United States: Elsevier Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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