دورية أكاديمية
HA-1-targeted T cell receptor (TCR) T cell therapy for recurrent leukemia after hematopoietic stem cell transplantation.
| العنوان: | HA-1-targeted T cell receptor (TCR) T cell therapy for recurrent leukemia after hematopoietic stem cell transplantation. |
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| المؤلفون: | Krakow EF; Fred Hutchinson Cancer Center, Seattle, Washington, United States., Brault M; Fred Hutchinson Cancer Research Center., Summers C; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., Cunningham TM; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., Biernacki MA; Fred Hutchinson Cancer Center, Seattle, Washington, United States., Black RG; Fred Hutchinson Cancer Center, Seattle, Washington, United States., Woodward KB; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., Vartanian N; Fred Hutchinson Cancer Center, Seattle, Washington, United States., Kanaan SB; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., Yeh AC; University of Washington School of Medicine, United States., Dossa RG; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., Bar M; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., Cassaday RD; Fred Hutchinson Cancer Center, Seattle, Washington, United States., Dahlberg A; Fred Hutchinson Cancer Center, Seattle, Washington, United States., Till BG; University of Washington School of Medicine, United States., Denker AE; ElevateBio Technologies, United States., Yeung CCS; Fred Hutchinson Cancer Center, Seattle, Washington, United States., Gooley TA; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., Maloney DG; University of Washington School of Medicine, United States., Riddell SR; University of Washington School of Medicine, United States., Greenberg PD; University of Washington School of Medicine, United States., Chapuis AG; University of Washington School of Medicine, United States., Newell EW; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., Furlan SN; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., Bleakley M; Fred Hutchinson Cancer Center, Seattle, Washington, United States. |
| المصدر: | Blood [Blood] 2024 Apr 29. Date of Electronic Publication: 2024 Apr 29. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مستخلص: | 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. (Copyright © 2024 American Society of Hematology.) |
| معلومات مُعتمدة: | K23 CA154532 United States CA NCI NIH HHS; P30 CA015704 United States CA NCI NIH HHS |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03326921 |
| تواريخ الأحداث: | Date Created: 20240429 Latest Revision: 20240524 |
| رمز التحديث: | 20240524 |
| DOI: | 10.1182/blood.2024024105 |
| PMID: | 38683966 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood.2024024105 |