2026-05-12 ワシントン大学セントルイス校
＜関連情報＞
- https://source.washu.edu/2026/05/gene-edited-stem-cell-transplant-shows-promise-for-aggressive-blood-cancers/
- https://www.nature.com/articles/s41591-026-04362-1
- https://ascopubs.org/doi/10.1200/PO-25-00556
CRISPR-Cas9を用いたCD33欠損同種造血幹細胞移植とゲムツズマブ・オゾガマイシン維持療法による急性骨髄性白血病（AML）治療：第1/2相臨床試験 CRISPR−Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a phase 1/2 tria
John F. DiPersio,Guenther Koehne,Nirali N. Shah,Léa Bernard,Hyung C. Suh,Divya Koura,Roni Tamari,Muhammad Umair Mushtaq,Joseph Maakaron,Joseph Rimando,Vanessa E. Kennedy,Sagar S. Patel,Chad Hudson,Michael R. Loken,Christopher A. Slapak,Deborah M. Lloyd,Darren A. Stanizzi,Melissa M. Lee-Sundlov,Sanjana Thosar,Guy Mundelboim,Guangwu Guo,Huanying Gary Ge,Bin E. Li,Juliana Xavier-Ferrucio,… Brenda W. Cooper
Nature Medicine Published:12 May 2026
DOI:https://doi.org/10.1038/s41591-026-04362-1
Abstract
Patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are likely to relapse despite allogenic hematopoietic cell transplantation (HCT). Post-HCT preventative maintenance can be limited by toxicity toward the normal donor cells. Tremtelectogene empogeditemcel (trem-cel) is a CRISPR–Cas9 gene-edited allogeneic HCT product lacking CD33, designed to shield the donor graft from cytotoxicity of subsequent CD33-targeted therapies such as gemtuzumab ozogamicin (GO). In this multicenter, phase 1/2a, open-label study, adult patients with AML/MDS with high relapse risk received trem-cel after myeloablative conditioning followed by GO maintenance (0.5–2.0 mg m−2 day 1 per 28-day cycles). Patients receiving trem-cel were assessed for the primary safety endpoint of neutrophil engraftment by day 28 and secondary endpoints including time to neutrophil engraftment, incidence of graft-versus-host disease and graft failure, transplant-related mortality, percentage of CD33-negative myeloid cells and survival. Patients receiving trem-cel and GO were assessed for the additional secondary endpoints of safety of maintenance GO with trem-cel and pharmacokinetics of GO after trem-cel transplant. All 30 patients receiving trem-cel achieved the primary safety endpoint of neutrophil engraftment by day 28 with a median engraftment time of 10 days (95% confidence interval: 9–10). Nineteen patients received GO maintenance in phase 1 dose escalation (n = 15) and in phase 2 dose expansion (n = 4). The trial was stopped early, and this is the final report on the trial including the completed phase 1 portion. GO treatment was safely tolerated up to the recommended phase 2 dose of 2 mg m−2, and no prolonged high-grade cytopenias were observed. The most common adverse events were cytopenias and infections. Three cases of transplant-related mortality were observed due to renal failure, sepsis and sinusoidal obstruction syndrome, respectively. In summary, trem-cel demonstrated safe, rapid, robust engraftment, and GO maintenance was administered without prolonged hematologic toxicity. ClinicalTrials.gov identifier: NCT04849910.
CD33を欠損するCRISPR/Cas9遺伝子編集同種移植片であるTrem-Celを用いた移植後、ドナー由来の抗CD33キメラ抗原受容体T（VCAR33）を投与したTP53変異型AMLの寛解 Remission of TP53-Mutant AML After Transplantation With Trem-Cel, a CRISPR/Cas9 Gene-Edited Allograft Lacking CD33, Followed by a Donor-Derived Anti-CD33 Chimeric Antigen Receptor T (VCAR33)
Guenther Koehne, MD, PhD, Muhammad U. Mushtaq, MD, Lori S. Muffly, MD, Manuel Menes, MD, Jacques Azzi, MD, Lea Bernard, MD, Brenda Cooper, MD, … Show All … , and John F. DiPersio, MD, PhD
JCO Precision Oncology Published:October 23, 2025
DOI:https://doi.org/10.1200/PO-25-00556
